The new england journal of medicine established in 1812 Treatment of Hypertension in Patients 80 Years Nigel S. Beckett, M.B., Ch.B., Ruth Peters, Ph.D., Astrid E. Fletcher, Ph.D., Jan A. Staessen, M.D., Ph.D., Lisheng Liu, M.D., Dan Dumitrascu, M.D., Vassil Stoyanovsky, M.D., Riitta L. Antikainen, M.D., Ph.D., Yuri Nikitin, M.D., Craig Anderson, M.D., Ph.D., Alli Belhani, M.D., Françoise Forette, M.D.,
Paediatric rhinitis: position paper of the european academy of allergy and clinical immunology
Paediatric rhinitis: position paper of the EuropeanAcademy of Allergy and Clinical Immunology G. Roberts1,2, M. Xatzipsalti3, L. M. Borrego4,5, A. Custovic6, S. Halken7, P. W. Hellings8,N. G. Papadopoulos9, G. Rotiroti10,11, G. Scadding10, F. Timmermans12 & E. Valovirta13 1David Hide Asthma and Allergy Research Centre, St Mary's Hospital, Isle of Wight; 2NIHR Respiratory Biomedical Research Unit,University Hospital Southampton NHS Foundation Trust and University of Southampton Faculty of Medicine, Southampton, UK; 3First Department of Pediatrics, P. & A. Kyriakou Children's Hospital, Athens, Greece; 4Faculty of Medical Sciences, Department of Immunology, NOVA, CEDOC, New University of Lisbon, Lisbon; 5Immunoallergy Department, CUF Descobertas Hospital, Lisbon, Portugal; 6Manchester Academic Health Science Centre, NIHR Respiratory and Allergy Clinical Research Facility, The University of Manchester, University Hospital of South Manchester NHS Foundation Trust, Manchester, UK; 7Hans Christian Andersen Children's Hospital, Odense University Hospital, Odense, Denmark; 8Department of Otorhinolaryngology, Head and Neck Surgery, University Hospitals of Leuven, Catholic University of Leuven, Leuven, Belgium; 9Allergy Department, 2nd Pediatric Clinic, University of Athens, Athens, Greece; 10Royal National Throat Nose and Ear, Hospital – Part of UCL Hospitals NHS Foundation Trust, London; 11Royal FreeHospital NHS Foundation Trust, London, UK; 12Nederlands Anafylaxis Netwerk, Dordrecht, the Netherlands; 13Terveystalo Turku, Allergy Clinic, University of Turku, Turku, Finland To cite this article: Roberts G, Xatzipsalti M, Borrego LM, Custovic A, Halken S, Hellings PW, Papadopoulos NG, Rotiroti G, Scadding G, Timmermans F, Valovirta E. Paediatric rhinitis: position paper of the European Academy of Allergy and Clinical Immunology. Allergy 2013; DOI: 10.1111/all.12235.
adolescents; allergy; children; paediatric; Rhinitis is a common problem in childhood and adolescence and impacts nega- tively on physical, social and psychological well-being. This position paper, pre- pared by the European Academy of Allergy and Clinical Immunology Taskforce Professor Graham Roberts, Paediatric on Rhinitis in Children, aims to provide evidence-based recommendations for the Allergy and Respiratory Medicine, University diagnosis and therapy of paediatric rhinitis. Rhinitis is characterized by at least Child Health (MP803), University Hospital two nasal symptoms: rhinorrhoea, blockage, sneezing or itching. It is classified as Southampton NHS Foundation Trust, allergic rhinitis, infectious rhinitis and nonallergic, noninfectious rhinitis. Similar Tremona Road, Southampton SO16 6YD, symptoms may occur with other conditions such as adenoidal hypertrophy, septal deviation and nasal polyps. Examination by anterior rhinoscopy and allergy tests Tel.: +44 (0) 2380796160 may help to substantiate a diagnosis of allergic rhinitis. Avoidance of relevant Fax: +44 (0) 2380878847 allergens may be helpful for allergic rhinitis (AR). Oral and intranasal antihis- tamines and nasal corticosteroids are both appropriate for first-line AR treat- Accepted for publication 6 July 2013 ment although the latter are more effective. Once-daily forms of corticosteroidsare preferred given their improved safety profile. Potentially useful add-on ther- apies for AR include oral leukotriene receptor antagonists, short bursts of anasal decongestant, saline douches and nasal anticholinergics. Allergen-specific Edited by: Wytske Fokkens immunotherapy is helpful in IgE-mediated AR and may prevent the progres-sion of allergic disease. There are still a number of areas that need to be clari-fied in the management of rhinitis in children and adolescents.
Rhinitis is a common problem in childhood and adolescence (1, 2). The burden associated with rhinitis is often ignored as AR, allergic rhinitis; ARIA, Allergic Rhinitis and its Impact on Asthma; CSF, cerebrospinal fluid; EAACI, European Academy of it is frequently seen as just a common cold or just as trivial Allergy and Clinical Immunology; IgE, immunoglobulin E; ISAAC, as a cold. In reality, patients experience disruptive sneezing, International Study of Asthma and Allergies in Childhood; NSAID, itching, watery rhinorrhoea and nasal blockage. Other chil- nonsteroidal, anti-inflammatory drug; PFS, pollen–food syndrome; dren and adolescents may present atypically with cough or SCIT, subcutaneous injection immunotherapy; SIT, specific snoring. Rhinitis impacts negatively on physical, social and immunotherapy; SLIT, sublingual immunotherapy; SPT, skin prick psychological well-being (3, 4). The direct effect of symp- 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd
Paediatric rhinitis Roberts et al.
reviewed by invited external experts, members of the EAACIENT and Pediatric Sections and Executive Committee.
Definition and classification Rhinitis is defined as an inflammation of the nasal epitheliumand is characterized by at least two nasal symptoms: rhinor-rhoea, blockage, sneezing or itching. There are a number ofdifferent clinical presentations of rhinitis which overlap. Thecommonest form is ‘allergic rhinitis' (AR) (Box 1) signifyingsymptoms caused by exposure to an allergen to which apatient is sensitized, in other words, allergen driven. Tradi-tionally, this group would be classified as having AR on thebasis of rhinitis symptoms in the presence of sensitization (9).
Typical allergens include house dust mite, grass pollen, treepollen, weed pollens, cat, dog and moulds (10). In adults,there is evidence to suggest that this form of rhinitis may existdespite a lack of apparent specific sensitization due to localimmunoglobulin E (IgE) production in the nose, otherwiseknown as entopy (11). It is unclear whether or not this is alsoseen in children (12). Allergic rhinitis can be seasonal orperennial, according to the relevant allergen. The distinctionbetween seasonal and perennial is not globally applicable, and Figure 1 Paediatric rhinitis taskforce logo.
therefore, it has been revised by the Allergic Rhinitis and itsImpact on Asthma (ARIA) group (9). Based on duration ofsymptoms, ARIA subdivides AR into intermittent or persis- toms, indirect effect of sleep disturbance with consequent tent (9). Both approaches have their value, seasonal–perennial daily fatigue and the use of antihistamines (5) all result in is useful for describing specific seasonal relationships with impaired school performance (6). The impact extends to the allergen exposure, whilst the ARIA approach is useful both rest of the family (7).
for describing how the rhinitis manifests in terms of symp- This position paper has been prepared by the European toms, its effects on quality of life and suggests the treatment Academy of Allergy and Clinical Immunology (EAACI) approach. Allergic Rhinitis and its Impact on Asthma also Taskforce on Rhinitis in Children (Fig. 1). The taskforce was usefully divides AR severity into mild, moderate and severe initiated as at present, there are no guidelines that specifically according to its impact on quality of life (13).
focus on paediatric rhinitis despite the huge burden of rhini- The second form of rhinitis is infectious rhinitis, usually sec- tis in childhood and adolescence as well as the differences ondary to a viral infection. There is some overlap between from adult rhinitis. The paper uses the terms children and allergic and infectious rhinitis in that atopic children with or childhood to cover patients up to 18 years of age unless spe- without allergic rhinitis can also present with an infectious rhi- cific age groups are mentioned. The position paper aims to nitis. Such atopic individuals may have an exaggerated provide evidence-based recommendations for diagnosis and response to viral upper respiratory tract infections; however, therapy. The breadth of rhinitis is encompassed although, for only indirect data support this (14).
brevity, the therapy section focuses on allergic rhinitis. A sys- Finally, there is a nonallergic, noninfectious group of other tematic extensive literature search was undertaken using disorders that may present with rhinitis including those asso- MEDLINE and EMBASE (search terms: rhinitis, prevalence, ciated with exposure to irritants, hormonal dysfunction and diagnosis and differential diagnosis, comorbidity, education, specific medications (Box 1).
pathophysiology, presentation, quality of life and treatment;restricted to children) and Cochrane Library in September Prevalence and epidemiology 2010 for the previous 5 years. The literature search returned4955 references that were reviewed to remove case reports The International Study of Asthma and Allergies in Child- and nonsystematic reviews to give 589 that were reviewed as hood (ISAAC) phase three studies (1999–2004) revealed an part of the taskforce. Members were also free to add other average prevalence of rhinitis of 8.5% (range 1.8–20.4%) in papers from before 2005. An updated search was undertaken 6- to 7-year-old children and 14.6% (1.4–33.3%) for 13- to in June 2012, it returned another 2913 references of which 63 14-year-old children (15). A worldwide increase in reported were reviewed in detail. Although a systematic review of the rhinitis prevalence was observed since the identical phase evidence was undertaken, only the highest available evidence one studies (1991–8) but with large variations between for each issue is presented here. The recommendations in this centres (16). International Study of Asthma and Allergies in document are labelled to indicate the grade of recommenda- Childhood defines current rhinitis on the basis of a positive answer by parents to ‘In the past 12 months, have you (has 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd Roberts et al.
Paediatric rhinitis Box 1: Classification of rhinitis causation in children Rhinitis symptoms that are associated with exposure to an allergen to which Allergic rhinitis
the patient is sensitized.
Secondary to infection Infectious rhinitis
Irritant exposure (eg exhaled tobacco smoke), gastroesophageal reflux and in older children, hormonal (hypothyroidism, pregnancy), drug- infectious rhinitis
induced (eg beta-blockers, contraceptives, NSAID), neurogenic or Different pathophysiologies may co-exist, particularly allergic rhinitis and infectious rhinitis. See Box 4 for conditions that may mimic rhinitis.
your child) had a problem with sneezing or a runny or blocked (25). AR can present less clearly, particularly in young chil- nose, when you (he or she) DID NOT have a cold or "the dren. Recommendations (D) for the recognition of rhinitis flu"?'(17). This question assumes that the respondent can cor- are presented in Box 2.
rectly identify a cold or ‘flu', for example, some children may Infectious rhinitis can be acute, commonly precipitated by only have significant symptoms with a combination of both a viral infection, or chronic, caused more often by bacteria allergic inflammation and a coexisting viral infection. This is and occasionally fungi. Children can typically have up to 11 a particularly issue in the preschool age (18). Furthermore, upper respiratory tract infection episodes per year in infancy, ISAAC uses the presence of coexisting itchy eyes to identify eight episodes at preschool age and four at school age (26), allergic rhinitis although this is probably more relevant for and 0.2–2% of these develop into clinically important bacte- pollen-induced rather than rhinitis driven by perennial aller- rial sinus infection (27). A chronic mucopurulent discharge gens such as house dust mite. The ISAAC questions have not suggests a rhinosinusitis of infective origin (28) (C). This may been well validated in a paediatric population (17).
be secondary to other pathologies, such as adenoidal hyper- There are a few studies looking at the natural history of trophy, anatomical abnormalities, primary immunodeficiency, rhinitis in childhood. The 1989 Isle of Wight birth cohort of primary ciliary dyskinesia or cystic fibrosis (28).
1456 children had prevalences of 2.8 and 11.8% at 4 and Nonallergic, noninfectious rhinitis is typically a chronic 18 years for rhinitis in nonsensitized individuals with figures of presentation that does not fit into an allergic rhinitis or infec- 3.4 and 27.3% for those who were sensitized (19). There was a tious rhinitis pattern of symptoms. This should prompt the male predominance of allergic rhinitis and female predomi- search for other causes (Box 1).
nance of nonallergic rhinitis during adolescence. The MASstudy followed up 467 children until 13 years and showed simi- Presentations associated with rhinitis comorbidities lar frequency of rhinitis (20). Allergic rhinitis, but not nonaller-gic rhinitis, in early childhood is a risk factor for developing In childhood, the presentation of rhinitis can frequently asthma in later childhood (21) and adulthood (22).
relate to its associated comorbidities (Box 3). The nose isanatomically and functionally linked to the eyes, paranasalsinuses, nasopharynx, middle ear, larynx and lower airway, Presentation and associated comorbidities and so, presenting features may be conjunctivitis, chroniccough, mouth breathing, nasal speech and snoring with or Classic symptoms and signs without obstructive sleep apnoea.
Classic symptoms and signs of allergic rhinitis are intermit- Allergic conjunctivitis is reported as the commonest com- tent or persistent nasal obstruction, rhinorrhoea (anterior or orbidity associated with AR (16, 29). It is characterized by posterior), pruritus and sneezing (23). All these impact nega- intense eye itching, conjunctival hyperaemia, watering eyes tively on quality of life (24). Symptoms occur generally and occasional peri-orbital oedema.
within minutes after allergen exposure and may last for hours Chronic allergic inflammation of the upper airways can after an isolated exposure. ‘Allergic shiners' (darkened lower cause lymphoid hypertrophy leading to prominence of the eyelid due to chronic congestion) are also often present, and adenoidal and tonsillar tissue. In a case–control study of 600 their darkness correlates with disease chronicity and severity children aged 4–9 years, more adenoidal hypertrophy was seen 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd Paediatric rhinitis Roberts et al.
Box 2: Recognizing rhinitis in childhood (D) Rhinorrhoea – clear or discoloured discharge, sniffing
Pruritus - nose rubbing, the "allergic salute", "allergic crease",
"sneeze", may be associated with complaints of an itchy mouth or and signs
throat in older children of rhinitis
Congestion - mouth breathing, snoring, sleep apnoea, allergic shiners
Eustachian tube dysfunction - ear pain
on pressure changes (eg flying), reduced
hearing, chronic otitis media with effusion
Cough – often mislabelled as asthma
Poorly controlled asthma – may co-exist with asthma
Sleep problems - tired, poor school performance, irritability
Prolonged and frequent respiratory tract infections
Rhinosinusitis - catarrh, headache, facial
pain, halitosis, cough, hyposmia
Pollen-food syndrome, particularly with
pollen driven allergic rhinitis
Box 3: Recognizing comorbidities of rhinitis in childhood (D) Ask about a history of red, itchy, watery eyes, eye rubbing Eye examination looking for signs of conjunctivitis Ask about any history of cough, wheeze, shortness of breath, exercise-induced bronchospasm Examine the chest – wheeze, hyperexpansionAssess peak expiratory flows, spirometry in older children preferably with reversibility testing with beta-2 agonists If in doubt, undertake an exercise, mannitol or methacholine challenge test Ask about any speech and language delay, increasing volume of TV, shouting, poor concentration, failing performance at school, Examine the ears – pneumatic otoscopy if possible, Weber and Rinne testsTympanoscopy for evaluation of tympanic membrane and middle ear Whisper test for screening of otitis media with effusion and hearing loss Audiometry in older children – pure tones, speech Ask about a history of nasal obstruction or discharge (purulent) with or without hyposmia, headache, facial pain or cough.
Undertake nasendoscopy in older children CT scan/sinus X-rays not recommended unless there are complications or failed therapy, unilateral symptoms or severe disease unresponsive to medical therapy Enquire about any history of disturbed sleep, snoring, apnoea, tiredness, irritability Assess nasal airway – spatula misting, nasal inspiratory peak flow, visual examination of nostrils and nasendoscopy in olderchildren to view nasal airway and adenoids Consider sleep study Pollen–food syndrome Ask about any oral pruritus with symptoms with (not cooked or frozen) foods such as apples Skin prick tests – seldom necessary to perform skin prick tests, and if so, it should be by prick-prick test with fresh foods andonly with the incriminated fruit as nonclinically relevant positivity could be elicited.
2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd Roberts et al.
Paediatric rhinitis in those with rhinitis, and it was suggested that this was driven charge, pain or recurrent epistaxis may suggest other diagno- by localized nasal inflammation (30). There is a significant ses (see differential diagnosis section below). Examination of increase in adenoidal size during the pollen season in children the nose is essential and should always be carried out, princi- with pollen-driven rhinitis (31). In a case series of 93 children pally to rule out alternatives such as nasal polyps (49) (D).
aged 2–10 years referred to a sleep laboratory for polysomnog- In daily practice, diagnosis is usually based on a suggestive raphy, sleep apnoea–hypopnoea syndrome was strongly associ- clinical history supported by examination by anterior rhinos- ated with the clinical history of nasal obstruction and AR (32).
copy demonstrating swollen mucosa (49) and a small number Chronic middle ear effusion and eustachian tube dysfunction, of IgE sensitization tests (SPT or specific IgE), in accordance potentially causing hearing impairment, are associated with with the history, population and region, which can suggest rhinitis (33–35). Local production of nonspecific and specific an allergic origin of the symptoms (D) (50). Where the diag- IgE against both environmental allergens and staphylococcal nosis is in doubt, nasal provocation testing can be utilized enterotoxin antigens may be involved in ongoing allergic although this has not been standardized (49, 51) (C).
inflammation observed in the adenoidal lymphatic tissue fromatopic children (12, 36).
Defining the presence of allergy Allergic sensitization can be defined as a positive skin test or Other comorbidities allergen-specific serum IgE. Measurement of total serum IgE has little value in assessing allergic aetiology of rhinitis in Asthma frequently coexists with AR being seen in half to childhood. The presence of sensitization is a major risk factor three quarter of children and teenagers with asthma in a for AR in children (19, 51). Outdoor allergens constitute a range of studies (37–40). Asthma is similarly associated with risk of seasonal rhinitis, whereas indoor allergens are associ- nonallergic rhinitis as demonstrated by the COPSAC high- ated with perennial rhinitis (52). The information on absence risk birth cohort (41). Allergic rhinitis is one of the risk of sensitization can be clinically very valuable potentially rul- factors for the development of asthma, and its signs and ing out a diagnosis of AR. The negative predictive value may symptoms often precede those of asthma (22). In an interna- be as high as 95% in a clinic population, and false negatives tional survey involving 8 countries in Europe and Asia, 76% are associated with local specific IgE production, particularly of children had pre-existing symptoms of AR when asthma in young children who have recently become symptomatic was first diagnosed (42). Allergic rhinitis also increases the (12). Additionally, a proportion of children with positive tests risk of asthma hospitalization. In a cross-sectional study have no symptoms and many children with symptoms of rhi- nitis are sensitized to allergens that do not give rise to the prevalence of AR was high and in combination with asthma symptoms (10). So, a positive allergen-specific IgE test alone severity constituted the major risk factor for emergency care does not confirm the allergic origin of the symptoms, and attendance (43). Viral upper respiratory tract infection results must be interpreted in the context of the clinical his- together with allergic sensitization and allergen exposure has tory (C). Quantification of specific IgE antibodies or the size been demonstrated to synergistically increase the risk of of wheal following skin testing can improve the specificity of emergency care with asthma (44). The presence of a cough in these tests in the assessment of airway diseases in childhood association with rhinitis and postnasal drip may falsely (53–55), and in practical terms, quantification of sensitization suggest a diagnosis of asthma (45).
offers more information to the clinician than simple presenceor absence of atopy (C).
Recent studies employing a molecular diagnostic approach Eczema and rhinitis frequently coexist in all age groups (46).
suggest that measurement of IgE response to specific aller-genic components may be more useful in determining clini- Pollen–food syndrome cally relevant sensitization to a specific pollen (56) and in Allergic rhinitis can be associated with pollen–food syndrome predicting food allergy than currently used skin or blood (PFS). Symptoms of oral pruritus and swelling occur due to tests based on whole extracts (57–59); this approach may cross-reactivity between aeroallergens, such as birch pollen, provide new tools for the assessment of children with symp- and fruits and vegetables such as apple (47). There are lim- toms suggestive of AR.
ited paediatric data focusing on this link although one studysuggests that a quarter of 8 year olds with AR are affected Other investigations Further investigations may be required to evaluate other pos-sible diagnoses, especially in cases of treatment failure (49) (D). Measurement of nasal mucociliary clearance and nasal Clinical history, including type, duration and frequency of nitric oxide may be useful in diagnosing primary ciliary dys- symptoms and exacerbating factors (see Box 1), is the corner- kinesia (60) (C). Nasal endoscopy may be useful for visualiz- stone for diagnosing and characterizing rhinitis in children ing polyps (D). Acoustic rhinometry can reveal a reduction (49) (D). Specific findings such as unilateral symptoms, nasal in the cross-sectional diameter of the nasal cavity at the level obstruction without other symptoms, mucopurulent dis- of the nasopharynx (49) (C). Lateral radiographs can be used 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd Paediatric rhinitis Roberts et al.
to evaluate the nasopharyngeal airway, and computer tomog- may occur in children and induce impaired nasal breathing, raphy may be helpful in the diagnosis of chronic rhinosinus- often unilateral in nature. Two thirds of children with cleft itis (49) (D). It may be necessary to utilize other tests to lip complain of nasal obstruction due to nasal septal devia- evaluate potential coexisting medical problems such as tion and the frequently associated stenosis of the nasal ves- asthma (Box 3).
tibulum. Rare conditions like choanal atresia or stenosis ofthe piriform aperture should not be overlooked in nasalobstruction in children. Nasal polyps in children impairing Differential diagnosis nasal breathing are rare (27), warranting investigations for The differential diagnosis of rhinitis (Box 4) in children can cystic fibrosis and/or primary ciliary dyskinesia or an enceph- best be approached using a symptom-based and age-related alocoele if unilateral polyp (D). Rarely, nasal obstruction differential diagnosis (D). These need to be particularly con- may be due to a malignancy.
sidered when symptoms do not respond to therapy (61).
Colour of nasal secretions Nasal obstruction The colour of nasal secretions provides a first diagnostic clue to Nasal obstruction in children may be the result of mucosal the nature of the underlying pathology (D). Transparent secre- pathology and/or anatomical abnormalities. Nasal obstruc- tions are seen initially in viral common colds, in AR and in the tion is often the presenting symptom of rhinitis in preschool rare condition of leakage of cerebrospinal fluid (CSF). Thick- children, with open mouth breathing, snoring and nasal ened and often discoloured mucus is found in the nasal cavity secretions. However, adenoidal hypertrophy is a common of patients with adenoidal hypertrophy, recurrent adenoiditis disorder inducing similar symptoms. Severe septal deviations and/or rhinosinusitis and in the later stages of the common Box 4: Dierential diagnosis of rhinitis in children (D) Diagnosis Pre-school
Obstruction without Choanal atresia
other features of or stenosis
allergic rhinitis Persisting mucopurlent discharge deficiency
Unilateral nasal "polyp" Mouth breathing, discoloured nasal Adenoidal
secretions, snoring in the absence hypertrophy
of other features of allergic rhinitis Unilateral discoloured Foreign body
nasal secretions, foul smell Discoloured nasal secretions, headache, facial pain, poor smell, halitosis, cough Bilateral nasal polyps, poor smell, chest symptoms, symptoms Cystic fibrosis
of malabsorption, failure to thrive Primary ciliary
Persisting mucopurlent discharge without respite between "colds", bilateral dyskinesia
stasis of mucus and secretions at the nasal floor, symptoms from birth CSF leakage
Colourless nasal discharge often with a history of trauma Recurrent epistaxis with minimal trauma Obstruction in the absence of other Septal deviation
features of allergic rhinitis 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd Roberts et al.
Paediatric rhinitis cold which is a viral rhinosinusitis. Sinusitis in children is as conclusive due to their small size and design (65) (D).
always associated with inflammation of the nasal cavity; hence, There is insufficient evidence on pet allergen avoidance in the term ‘rhinosinusitis' is preferred. Chronic severe rhinosi- AR but it would be clinical practice to recommend avoidance nusitis may also be associated with primary ciliary dyskinesia, cystic fibrosis and humoral and/or cellular immune dysfunc-tion. These conditions should be screened for in children with persistent and severe sinonasal symptoms (D). Children withunilateral discoloured secretions should be evaluated for Oral and intranasal antihistamines foreign bodies (D).
Both oral and intranasal second-generation antihistaminesare equally effective for AR (67–73) (A). Oral ones may bebetter tolerated, whilst intranasal antihistamines have a more Smell dysfunction rapid onset of action (74). First-generation antihistamines Smell dysfunction represents a typical feature of rhinosinusitis should no longer be used, given their unfavourable therapeutic (27) and has not been well studied in children. It is, however, index (24, 74, 75) (B). In a minority of children, second-genera- known that children with severe rhinosinusitis and nasal tion ones may also cause sedation (76) with perhaps the excep- polyps, as in primary ciliary dyskinesia or cystic fibrosis, may tion of fexofenadine (74).
experience hyposmia or anosmia, often without major subjec-tive impairment. The rare Kallmann syndrome is character- ized by anosmia due to hypoplasia of the olfactory bulb (62).
Corticosteroids address the inflammatory component of AR,and results from a large number of well-designed studies wouldrecommend their use in children and adolescents from 2 years (77–91) (A). The recent Cochrane review (92) failed to find evi- Headache in children is a manifestation of rhinosinusitis dence supporting the effectiveness of intranasal corticosteroids rather than rhinitis (49).
but it excluded all the recent high-quality randomized con-trolled trials as they allowed rescue medication. Several studieshave shown that the effects of mometasone, fluticasone and ciclesonide commence within a day of starting therapy (93).
Minor epistaxis in children is common in AR or in children Intranasal corticosteroids probably also improve coexisting with congestion of the vessels at the locus Kiesselbach. Exces- asthma (94–96) (A), and fluticasone furoate and mometasone sive nasal bleedings warrant a nasal endoscopy excluding a may be effective for conjunctivitis (77, 82, 97) (B).
nasopharyngeal angiofibroma (63) and coagulopathies (D).
Newer, once-daily products (e.g. fluticasone propionate (98),mometasone (99–101), fluticasone furoate nasal spray (82)) are preferred as these have been shown, unlike beclometha- Cough is an important manifestation of rhinitis due to post- sone, not impair growth velocity albeit only after a year of nasal drip and stimulation of cough receptors in nasal cavity, therapy (102, 103) (A). This is probably due to the much pharynx and larynx. Other diagnoses should be considered lower systemic bioavailability of the newer products (Fig. 2).
when there are no other features of rhinitis or where it fails Nasal perforation and epistaxis have been described as risks to respond to therapy (64). Examples are recurrent upper air- of nasal corticosteroids but there are no systematically way infections, pertussis, habit cough, aspiration bronchiecta- collected data on these adverse effects in the literature.
sis, foreign body or tuberculosis; asthma is unlikely withoutother symptoms of bronchospasm.
Systemic corticosteroidsA few studies on systemic corticosteroid therapy have beenperformed in adults. In adults, a daily 7.5 mg prednisolone dose was marginally effective, whereas a 30 mg dose was Apart from antibiotics in bacterial infectious rhinitis, we cur- effective but also associated with systemic side-effects (104).
rently have no effective therapy for infectious rhinitis, and Depot corticosteroid injections are associated with local atro- so, in this section, we will focus on AR. The management of phy of the skin and muscles, reduced bone mineralization AR includes avoidance of relevant allergens, symptomatic and impaired growth (105). If systemic corticosteroid treat- treatment and specific immunotherapy.
ment is necessary in children, a short course with 10–15 mgoral prednisolone a day for 3–7 days for school-age childrenmay be sufficient (D).
Allergen avoidance Outdoor allergens, such as pollen, cannot be completely Oral leukotriene receptor antagonist avoided. For indoor allergens, avoidance should be more Montelukast monotherapy is effective in both seasonal and possible. Few studies have investigated the effect of effective perennial AR in two well-designed, but small, paediatric house dust mite avoidance in paediatric AR. In general, they studies (106, 107) as well as in two meta-analyses dominated have failed to demonstrate a benefit but cannot be described by adult studies (108, 109) (A).
2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd Paediatric rhinitis Roberts et al.
Fluticasone Mometasone Fluticasone Budesonide Beclometasone Triamcinolone Flunisolide Figure 2 Systemic bioavailability of different nasal corticosteroids.
Nasal anticholinergics as add-on therapy with nasal corticosteroids (73, 74, 118, Anticholinergics have been reported to be effective in con- 120)(B). Given these data, we propose the approach to phar- trolling watery nasal discharge in the elderly (C) but not for macological management described in Fig. 3. We would sug- itching, sneezing or obstruction (110). It is rarely prescribed gest that topical nasal corticosteroids are the appropriate in children.
first-line therapy in moderate-to-severe AR, especially whencongestion is the predominant complaint, but antihistamines Nasal decongestants may be preferred in mild AR to minimize the exposure to Topical decongestants can be used for a few days for severe corticosteroid in children.
nasal obstruction but should only be used for a few days asprolonged use may lead to rebound swelling of the nasal Pharmacotherapy for nonallergic, noninfectious rhinitis mucosa (111) (C).
There are no high-quality data to formulate treatment recom-mendations in children with nonallergic, noninfectious rhini- Nasal sodium cromoglicate tis. Management should be directed by the underlying cause Intranasal sodium cromoglicate is an effective AR therapy (Box 1). Where this is not obvious, saline douches and/or albeit the trials are relatively old (112) (A), and repeated use topical corticosteroids should be tried first [D]. If symptoms several times a day renders concordance difficult.
continue, further investigation should be undertaken toexclude obstruction, topical antihistamine then short-term topical Saline douches are inexpensive and have been shown to be decongestants may be considered [D]. For watery rhinor- effective for rhinitis (113–115) (A). In patients with poorly rhoea, ipratropium may help [D]. There are adult controlled controlled, moderate-to-severe allergic asthma and AR, oma- study data to suggest that capsaicin may reduce symptoms lizumab has been found to be effective for both rhinitis and asthma (116). There is no convincing evidence for the efficacyof alternative medication for AR (117).
Relative effectiveness of different pharmacological approaches Allergen-specific immunotherapy (SIT) is the specific treat- in allergic rhinitis ment for IgE-mediated allergic disease in patients (124), and Assessing the relative efficacies of therapies and the potential this may utilize the subcutaneous or sublingual routes.
benefit of combining them is compromised by the lack ofstudies in the pre-adolescent age group. Nasal corticosteroids Indications and contraindications are more effective at controlling AR than either antihis- There should be a clear history of AR with evidence of a tamines or montelukast (73, 118–120) (B). All are more small number of clinically relevant sensitizations, in other effective than nasal cromoglicate (73) (B). Symptoms of con- words allergen-driven AR (125, 126) (D); this may limit its gestion are only effectively controlled by nasal corticosteroids use in the preschool children. The need for injections also (120) (B). In children, there are insufficient comparative data effectively limits the use of subcutaneous immunotherapy to determine whether antihistamines or montelukast is more to school-age children. Specific immunotherapy should be effective, although some studies indicate that antihistamines performed with a standardized allergen extract or prepara- are more effective for itching (121, 122). Antihistamines and tion registered or approved by the authorities (D). Therapy montelukast may provide some additional benefit when used should be initiated by a physician with training in the diag- 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd Roberts et al.
Paediatric rhinitis Trial of addiƟon of
anƟhistamine ± leukotriene
receptor antagonist to nasal
if well contr
AnƟhistamine, oral or
Figure 3 Approach to therapy for paediatric allergic rhinitis.
of action. **Reconsider diagnosis if not controlled within 1-2 weeks are potential entry points into therapeutic approach depend- (61). If less than 2 years of age and do not respond to antihista- ing on the severity of the rhinitis symptoms. For seasonal disease, mine within a week, reconsider diagnosis before stepping up ther- regular therapy should be commenced 2 weeks before the antici- apy. If poorly controlled, consider a short rescue course of a pated start of symptoms (150). *Oral antihistamines may be better decongestant or low-dose oral prednisolone to gain symptom con- tolerated, whilst intranasal antihistamines have a more rapid onset trol; topical ipratropium may be useful for rhinorrhoea.
nostic procedures, treatment and follow-up of allergic and repeated with a SLIT product using a placebo-controlled asthmatic children (127) (D). Significant concurrent disease, design (137). Two commercial grass products have received impaired lung function and severe asthma are contraindica- European market authorization for patients at least 5 years tions (125) (D).
of age (138, 139). Local oral reactions are experienced in upto three quarter of the patients but are mild to moderate, Subcutaneous injection immunotherapy (SCIT) self-resolve after a few minutes and usually disappear after a The 2007 Cochrane systematic review of SCIT (128) in AR few weeks therapy (129, 134, 140, 141). Severe adverse reac- demonstrates that it is effective although there were no tions have been seen but are very rare (142). There is concern accepted studies that were conducted exclusively in children.
about compliance with SLIT with sales data suggesting 44% Subcutaneous injection immunotherapy has been associated compliance in the first year, 28% in second year and 13% in with systemic reactions but it is generally well tolerated in chil- the third year (143) although regular clinic contact may dren (128, 129). There are also some nonblinded data to sug- improve this (144) (B). Again, adult data would suggest that gest that SCIT may alter the natural history of allergic disease 3 years of SLIT is sufficient, at least for pollens (145).
in childhood (130). Factors associated with severe adverseeffects are unstable asthma, elevated allergen exposure during therapy, concomitant diseases such as severe infections and Pharmacoeconomic models based on data provided by clini- inexperienced healthcare staff. There is some evidence to sug- cal trials and meta-analyses indicate that SIT is cost-efficient gest that antihistamine premedication may reduce the rate of (146). One of the few real patient cohort studies to investi- adverse effects (131) (B). Also, pretreatment with anti-IgE has gate cost-effectiveness of SCIT was performed in US children been used to reduce the rate of adverse reactions associated with allergic rhinitis; patients in the SCIT group incurred with updosing with SCIT (132) (A). There are no paediatric 33% lower healthcare costs (147, 148).
data addressing the question of how long SCIT should be con-tinued although adult data would suggest that 3 years is suffi- Compliance with therapy cient at least for pollens (133).
The compliance of children with rhinitis therapy has not been Sublingual immunotherapy (SLIT) well studied. Adherence to the use of nasal sprays may be The effectiveness of SLIT for AR has been evaluated in a suboptimal due to discomfort, particularly in young children number of systematic reviews. The 2011 review demonstrates (149). Further work is required in this area. Even when its effectiveness for pollen and house dust mite-driven rhinitis patients use their medication, it is critical that they know (134) (A). This review highlights the considerable heterogene- how to do so correctly, especially nasal medications and edu- ity between studies, not all preparations seem to be effective.
cation are essential (D). Reassurance of the patient and care- givers about the safety of nasal corticosteroids is almost described, both seem to be effective although the latter may certainly necessary, together with information about the take longer to impact on the symptoms (135). There are also nature of rhinitis, its comorbidities and complications and some nonblinded data to suggest that SLIT may prevent the the benefits of effective therapy.
development of asthma (136); these studies are now being 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd Paediatric rhinitis Roberts et al.
sidered the most effective therapeutic option for children Summary and conclusions with AR and nonallergic rhinitis with congestion. Add-on Rhinitis is a prevalent yet underappreciated paediatric prob- therapies are oral montelukast, intranasal anticholinergics lem. These are the first paediatric specific recommendations.
for nasal discharge and decongestants for severe nasal Many children present with typical nasal symptoms, such as obstruction. There are a number of unmet research needs in rhinorrhoea, blockage, sneezing or itching. Atypical presenta- tions usually relate to associated comorbidities such as approaches to control effectively the small but important asthma, eczema, pollen–food syndrome, sleep disorders and number of children with ongoing symptoms despite the use hearing problems. The commonest presentations are allergic of current medications.
rhinitis and infectious rhinitis. Other children have a nonaller-gic, noninfectious rhinitis usually associated with exposure to irritants, gastro-oesophageal reflux, hormonal dysfunction, We would like to acknowledge the support of EAACI in specific medications or simply idiopathic. A detailed compre- developing this position paper. We thank Ray Clarke, hensive clinical history supported by a thorough examination Wytske Fokkens and Helen Smith for providing expert of the nose is important to aid accurate diagnosis. A limited feedback on the final draft of the paper. We would also like number of allergy tests are useful to confirm or refute aller- to thank our EAACI ENT and Pediatric Section colleagues gic origins of symptoms. In case of treatment failure, further (in particular, Montserrat Alvaro Lozano, Carlo Caffarelli, investigations are required to exclude other possible diagno- Hans de Groot, Sten Dreborg, Lamia El Housseiny, Linus ses. A successful therapeutic approach to paediatric AR Grabenhenrich, Artur Gevorgyan, Ruperto Gonzalez-Perez, should involve a holistic approach to all the manifestations Maria Ibanez, Kaja Julge, Matthias Kramer, Stefania La with avoidance of relevant allergens where possible, pharma- Grutta, Susan Leech, Rita Miarakian, Joaquim Mullol, cotherapy with or without specific immunotherapy. Both oral Nicolas Nicolaou, Muge Ozcan, Celso Pereira, Nicole Pet- and intranasal antihistamines are appropriate for first-line rus, Rodrigos R Alves, Jorge Sanchez, Natacha Santos, treatment for AR, whilst intranasal corticosteroids are con- Esmeralda Shehu, Kirsten Skamstrup Hansen, Michael Soy-ka, Sanna Toppila-Salmi, Laura Vega, Ulrich Wahn, Mag-nus Wickman and Renata Zubrzycka) and the EAACIExecutive Committee for their helpful comments and sug- Box 5: Unmet research needs in rhinitis in children Randomized double-blind, placebo-controlled studies Author contributions focusing on potential for SIT to alter the natural history of allergy (e.g. development of further sensitization and The EAACI Pediatric Section, in collaboration with EA- ACI ENT and Asthma Sections, proposed the topic which Identification of patients in whom rhinitis will progress to was accepted by the EAACI Executive Committee. Each author drafted a section which GR edited into the final Generation of paediatric specific data for efficacy of SCIT document. All authors reviewed and discussed the final and cost-effectiveness of SIT document and approved the final version. The final ver- Evaluation of effective allergen avoidance as a useful sion was evaluated and endorsed by the EAACI Executive therapy for AR.
Evaluation of the potential value of component-resolved diagnosis and their health economics, in the evaluation of children with rhinitis.
Conflicts of interest Investigate the potential role of local IgE production in GR, SH and EV are investigators in the ALK-Abello funded Identifying patients with poor compliance and developing GAP SLIT asthma prevention study. NGP has received pay- educational and other strategies to address this.
ment for consultancy from ABBOTT, Novartis, Menarini, Development of effective therapy for the small but for lectures from MSD, URIACH, GSK, ALLERGOPHAR- important proportion of children with uncontrolled rhinitis MA, Stallergens, MEDA, for development of educational despite maximal therapy.
presentations from MSD, URIACH, MEDA and grants Role of viral infections in the aetiology of allergic rhinitis and from Nestle, MSD and Deviblis. GS has received research as cofactors in the development of symptoms with grants from GSK and ALK-Abello; honoraria for articles, allergen exposure.
consulting, lectures, chairing or advisory boards from ALK- Development and validation of improved epidemiological Abello, Capnia, Circassia, Church & Dwight, GSK, Groupo definitions of the different types of childhood rhinitis.
Uriach, Meda and Merck, Ono, Oxford Therapeutics and Controlled trials focused on noninfectious, nonallergic Shionogi; and travel funding from GSK. LMB has received rhinitis in childhood.
honoraria for lectures from MSD. GR, AC, PH and NP are Public education campaign to promote the recognition of members of the EAACI Executive Committee. FT is the allergic rhinitis in children as a major health problem.
director of the Nederlands Anafylaxis Netwerk.
2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd Roberts et al.
Paediatric rhinitis 1. Asher MI, Montefort S, Bjorkston B, Lai tion of the modified allergic rhinitis and its 25. Chen C, Lin Y, Wen C, Wang L, Lin K, C, Strachan D, Weiland S et al. World- impact on asthma (ARIA) severity classifi- Chiu S et al. Quantitative assessment of wide time trends in the prevalence of cation in allergic rhinitis children: the PED- allergic shiners in children with allergic symptoms of asthma, allergic rhinocon- RIAL study. Allergy 2012;67:1437–1442.
rhinitis. J Allergy Clin Immunol junctivitis, and eczema in childhood: 14. Corne JM, Lau L, Scott SJ, Davies R, ISAAC Phases One and Three repeat mul- Johnston SL, Howarth PH. The relation- 26. Greber C, Keil T, Kulig M, Roll S, Wahn ticountry cross-sectional surveys. Lancet ship between atopic status and IL-10 nasal U, Wahn V et al. History of respiratory lavage levels in the acute and persistent infections in the first 12 yr among children 2. The International Study of Asthma and inflammatory response to upper respiratory from a birth cohort. Pediatr Allergy Immu- Allergies in Childhood (ISAAC) Steering tract infection. Am J Respir Crit Care Med Committee. Worldwide variation in preva- 27. Fokkens W, Lund V, Mullol J. European lence of symptoms of asthma, allergic rhi- 15. Ant K, Pearce N, Anderson HR, Ellwood position paper on rhinosinusitis and nasal noconjunctivitis, and atopic eczema: P, Montefort S, Shah J. Global map of the polyps. Rhinol Suppl 2007;2007:1–136.
ISAAC. Lancet 1998;351:1225–1232.
prevalence of symptoms of rhinoconjuncti- 28. Fokkens WJ, Lund VJ, Mullol J, Bachert 3. Silva CHM, Silva T, Morales N, Fernandes vitis in children: The International Study of C, Alobid I, Baroody F et al. EPOS 2012: K, Pinto R. Quality of life in children and Asthma and Allergies in Childhood ISAAC European position paper on rhinosinusitis adolescents with allergic rhinitis. Braz Phase Three. Allergy 2009;64:123–148.
and nasal polyps 2012. A summary for J Otorhinolaryngol 2009;75:642–649.
16. Bjorksten B, Clayton T, Ellwood P, Stewart 4. Roberts G, Hurley C, Lack G. Develop- A, Strachan D. Worldwide time trends for ment of a quality-of-life assessment for the symptoms of rhinitis and conjunctivitis: 29. Bertelsen R, Lodrup C, Carlsen K. Rhinitis allergic child or teenager with multisystem Phase III of the International Study of in children: co-morbidities and phenotypes.
allergic disease. Journal of Allergy & Clini- Asthma and Allergies in Childhood. Pediatr Pediatr Allergy Immunol 2010;21:612–622.
cal Immunology 2003;111:491–497.
Allergy Immunol 2008;19:110–124.
30. Modrzynski M, Zawisza E. An analysis of 5. Vuurman EF, van Veggel LM, Uiterwijk 17. Online Manual. International Study of the incidence of adenoid hypertrophy in MM, Leutner D, O'Hanlon JF. Seasonal Asthma and Allergies in Childhood. http:// allergic children. Int J Pediatr Otorhinolar- allergic rhinitis and antihistamine effects on isaac.auckland.ac.nz/, accessed on 16th children's learning. Ann Allergy Asthma February 2013.
31. Modrzynski M, Zawisza E. The influence 18. Herr M, Clarisse B, Nikasinovic L, Fou- of birch pollination on the adenoid size in 6. Walker S, Khan W, Fletcher M, Cullinan cault C, Le Marec AM, Giordanella JP children with intermittent allergic rhinitis.
P, Harris J, Sheikh A. Seasonal allergic rhi- et al. Does allergic rhinitis exist in infancy? Int J Pediatr Otorhinolaryngol nitis is associated with a detrimental effect Findings from the PARIS birth cohort.
on examination performance in United 32. Ramos RTT, Daltro CHC, Gregorio PB.
Kingdom teenagers: case-control study.
19. Kurukulaaratchy RJ, Karmaus W, Raza A, OSAS in children: clinical and polysomno- J Allergy Clin Immunol 2007;120:381–387.
Matthews S, Roberts G, Arshad SH. The graphic respiratory profile. Braz J Otorhi- 7. Emin O, Mustafa S, Nedim S. Psychological influence of gender and atopy on the natu- stress and family functioning in mothers of ral history of rhinitis in the first 18 years of 33. Alles R, Parikh A, Hawk L, Darby Y, children with allergic rhinitis. Int J Pediatr life. Clin Exp Allergy 2011;41:851–859.
Romero JN, Scadding G. The prevalence 20. Keil T, Bockelbrink A, Reich A, Hoffmann of atopic disorders in children with chronic 8. Harbour R, Miller J. A new system for U, Kamin W, Forster J et al. The natural otitis media with effusion. Pediatr Allergy grading recommendations in evidence based history of allergic rhinitis in childhood.
guidelines. BMJ 2001;323:334–336.
Pediatr Allergy Immunol 2010;21:962–969.
34. Umapathy D, Alles R, Scadding G. A 9. Bousquet J, Khaltaev N, Cruz AA, Den- 21. Rochat MK, Illi S, Ege MJ, Lau S, Keil T, community based questionnaire study on burg J, Fokkens WJ, Togias A et al. Aller- Wahn U et al. Allergic rhinitis as a predic- the association between symptoms sugges- gic rhinitis and its impact on asthma ARIA tor for wheezing onset in school-aged chil- tive of otitis media with effusion, rhinitis 2008 update in collaboration with the dren. J Allergy Clin Immunol and asthma in primary school children. Int World Health Organization, GA2LEN and J Pediatr Otorhinolaryngol 2007;71:705–712.
Aller Gen. Allergy 2008;63:8–160.
22. Burgess J, Walters EH, Byrnes G, Mathe- 35. Chantzi FM, Kafetzis DA, Bairamis T, 10. Burbach GJ, Heinzerling LM, Edenharter son M, Jenkins M, Wharton C et al. Child- Avramidou C, Paleologou N, Grimani I G, Bachert C, Bindslev-Jensen C, Bonini S hood allergic rhinitis predicts asthma et al. IgE sensitization, respiratory allergy et al. GA(2)LEN skin test study II: clinical incidence and persistence to middle age: a symptoms, and heritability independently relevance of inhalant allergen sensitizations longitudinal study. J Allergy Clin Immunol increase the risk of otitis media with effu- in Europe. Allergy 2009;64:1507–1515.
sion. Allergy 2006;61:332–336.
11. Durham SR, Smurthwaite L, Gould HJ.
23. Scadding GK, Durham SR, Mirakian R, 36. Shin S, Choi G, Lee K, Kim S, Cho J, Local IgE production. Am J Rhinol Jones NS, Leech SC, Farooque S et al.
Park H. IgE response to staphylococcal BSACI guidelines for the management of enterotoxins in adenoid tissues from atopic 12. Shin S, Choi S, Hur G, Lee K, Kim S, Cho allergic and non-allergic rhinitis. Clin Exp children. Laryngoscope 2009;119:171–175.
J et al. Local production of total IgE and 37. Kurukulaaratchy RJ, Raza A, Scott M, specific antibodies to the house dust mite in 24. Juniper E, St ahl E, Doty R, Simons F, Williams P, Ewart S, Matthews S et al.
adenoid tissue. Pediatr Allergy Immunol Allen D, Howarth P. Clinical outcomes and Characterisation of asthma that develops adverse effect monitoring in allergic during adolescence; findings from the Isle 13. Montoro J, Del Cuvillo A, Mullol J, rhinitis. J Allergy Clin Immunol 2005;115: of Wight Birth Cohort. Respir Med Molina X, Bartra J, Davila I et al. Valida- 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd Paediatric rhinitis Roberts et al.
38. Hamouda S, Karila C, Connault T, 50. Bousquet J, Heinzerling L, Bachert C, 62. Vogl TJ, Stemmler J, Heye B, Schopohl J, Scheinmann P, De Blic J. Allergic rhinitis Papadopoulos NG, Bousquet PJ, Burney Danek A, Bergman C et al. Kallman syn- in children with asthma: a questionnaire- PG et al. Practical guide to skin prick tests drome versus idiopathic hypogonadotropic based study. Clin Exp Allergy in allergy to aeroallergens. Allergy hypogonadism at MR imaging. Radiology 39. Kurukulaaratchy RJ, Fenn M, Matthews S, 51. Melillo G, Bonini S, Cocco G, Davies RJ, 63. Sandoval C, Dong S, Visintainer P, Ozkay- Arshad SH. Characterisation of atopic and de Monchy JG, Frolund L et al. EAACI nak MF, Jayabose S. Clinical and laboratory non-atopic wheeze in 10 year old children.
provocation tests with allergens. Allergy features of 178 children with recurrent epistaxis. J Pediatr Hematol Oncol 40. Ballardini N, Kull I, Lind T, Hallner E, 52. Marinho S, Simpson A, Lowe L, Kissen P, Almqvist C, Ostblom E et al. Development Murray C, Custovic A. Rhinoconjunctivitis 64. Shields MD, Bush A, Everard ML, and comorbidity of eczema, asthma and rhi- in 5-year-old children: a population-based McKenzie S, Primhak R. Recommenda- nitis to age 12 years data from the BAMSE birth cohort study. Allergy 2007;62:385–393.
tions for the assessment and management birth cohort. Allergy 2012;67:537–544.
53. Simpson A, Tan VY, Winn J, Svensen M, of cough in children. Thorax 2008;63(Suppl 41. Chawes BL, Bonnelykke K, Kreiner-Moller Bishop CM, Heckerman DE et al. Beyond E, Bisgaard H. Children with allergic and atopy: multiple patterns of sensitization in 65. Nurmatov U, van Schayck CP, Hurwitz B, nonallergic rhinitis have a similar risk of relation to asthma in a birth cohort study. Am Sheikh A. House dust mite avoidance mea- asthma. J Allergy Clin Immunol J Respir Crit Care Med 2010;181:1200–1206.
sures for perennial allergic rhinitis: an 54. Marinho S, Simpson A, Soderstrom L, updated Cochrane systematic review.
42. Valovirta E, Pawankar R. Survey on the Woodcock A, Ahlstedt S, Custovic A.
impact of comorbid allergic rhinitis in Quantification of atopy and the probability 66. Custovic A, Wijk RG. The effectiveness of patients with asthma. BMC Pulm Med of rhinitis in preschool children: a popula- measures to change the indoor environment tion-based birth cohort study. Allergy in the treatment of allergic rhinitis and 43. Lasmar L, Camargos P, Ordones A, Gas- asthma: ARIA update in collaboration with par G, Campos E, Ribeiro G. Prevalence 55. Simpson A, Soderstrom L, Ahlstedt S, GA2LEN. Allergy 2005;60:1112–1115.
of allergic rhinitis and its impact on the use Murray CS, Woodcock A, Custovic A. IgE 67. Shah S, Nayak A, Ratner P, Roland P, of emergency care services in a group of antibody quantification and the probability Michael W. Effects of olopatadine hydro- children and adolescents with moderate to of wheeze in preschool children. J Allergy chloride nasal spray 06% in the treatment severe persistent asthma. J Pediatr Clin Immunol 2005;116:744–749.
of seasonal allergic rhinitis: a phase III, 56. Wickman M, Lilja G, Soderstrom L, Van multicenter, randomized, double-blind, 44. Murray CS, Poletti G, Kebadze T, Morris H, Ahlstedt S. Quantitative analysis of IgE active- and placebo-controlled study in J, Woodcock A, Johnston SL et al. Study antibodies to food and inhalant allergens in adolescents and adults. Clin Ther of modifiable risk factors for asthma exac- 4-year-old children reflects their likelihood erbations: virus infection and allergen expo- of allergic disease. Allergy 2005;60:650–657.
68. Bachert C, Kuna P, Sanquer F, Ivan P, sure increase the risk of asthma hospital 57. Valenta R, Twaroch T, Swoboda I. Com- Dimitrov V, Gorina MM et al. Comparison admissions in children. Thorax ponent-resolved diagnosis to optimize aller- of the efficacy and safety of bilastine 20 mg gen-specific immunotherapy in the vs desloratadine 5 mg in seasonal allergic 45. Plevkova J, Varechova S, Brozmanova M, Mediterranean area. J Investig Allergol Clin rhinitis patients. Allergy 2009;64:158–165.
Tatar M. Testing of cough reflex sensitivity Immunol 2007;17(Suppl 40):88–92.
69. Meltzer EO, Scheinmann P, Rosado Pinto in children suffering from allergic rhinitis 58. Nicolaou N, Murray C, Belgrave D, Poo- JE, Bachert C, Hedlin G, Wahn U et al.
and common cold. J Physiol Pharmacol rafshar M, Simpson A, Custovic A. Quanti- Safety and efficacy of oral fexofenadine in fication of specific IgE to whole peanut children with seasonal allergic rhinitis – a 46. Asher MI, Stewart AW, Wong G, Strachan extract and peanut components in predic- pooled analysis of three studies. Pediatr DP, Garcia-Marcos L, Anderson HR.
tion of peanut allergy. J Allergy Clin Immu- Allergy Immunol 2004;15:253–260.
Changes over time in the relationship 70. de Blic J, Wahn U, Billard E, Alt R, Puja- between symptoms of asthma, rhinocon- 59. Nicolaou N, Poorafshar M, Murray C, zon M. Levocetirizine in children: evi- junctivitis and eczema: a global perspective Simpson A, Winell H, Kerry G et al.
denced efficacy and safety in a 6-week from the International Study of Asthma Allergy or tolerance in children sensitized randomized seasonal allergic rhinitis trial.
and Allergies in Childhood (ISAAC).
to peanut: prevalence and differentiation Pediatr Allergy Immunol 2005;16:267–275.
Allergol Immunopathol 2012;40:267–274.
using component-resolved diagnostics.
71. Wahn U, Meltzer EO, Finn AF, Kowalski 47. Webber CM, England RW. Oral allergy J Allergy Clin Immunol 2010;125: ML, Decosta P, Hedlin G et al. Fexofena- syndrome: a clinical, diagnostic, and thera- dine is efficacious and safe in children (aged peutic challenge. Ann Allergy Asthma 60. Strippoli MP, Frischer T, Barbato A, Snij- 6–11 years) with seasonal allergic rhinitis.
ders D, Maurer E, Lucas JSA et al. Man- J Allergy Clin Immunol 2003;111:763–769.
48. Westman M, Stjarne P, Asarnoj A, Kull I, agement of primary ciliary dyskinesia in 72. Yang YH, Lin YT, Lu MY, Tsai MJ, van Hage M, Wickman M et al. Natural European children: recommendations and Chiang BL. A double-blind, placebo-con- course and comorbidities of allergic and clinical practice. Eur Respir J trolled, and randomized study of loratadine nonallergic rhinitis in children. J Allergy (Clarityne) syrup for the treatment of Clin Immunol 2012;129:403–408.
61. Hellings PW, Fokkens WJ, Akdis C, allergic rhinitis in children aged 3 to 49. Scadding G, Hellings P, Alobid I, Bachert Bachert C, Cingi C, Dietz de Loos D et al.
12 years. Asian Pac J Allergy Immunol C, Fokkens W, van Wijk R et al. Diagnos- Uncontrolled allergic rhinitis and chronic tic tools in Rhinology, EAACI position rhinosinusitis: where do we stand today? 73. Benninger M, Farrar J, Blaiss M, Chipps B, paper. Clin Transl Allergy 2011;1:2.
Ferguson B, Krouse J et al. Evaluating 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd Roberts et al.
Paediatric rhinitis approved medications to treat allergic rhini- for the treatment of seasonal allergic rhini- 97. Bielory L. Ocular symptom reduction in tis in the United States: an evidence-based tis in adults and adolescents. Allergy patients with seasonal allergic rhinitis review of efficacy for nasal symptoms by Asthma Proc 2007;28:216–225.
treated with the intranasal corticosteroid class. Ann Allergy Asthma Immunol 85. Ratner P, Wingertzahn M, Van B, Hampel mometasone furoate. Ann Allergy Asthma F, Darken P, Shah T. Efficacy and safety 74. Simons FE, Simons KJ. Histamine and H1- of ciclesonide nasal spray for the treatment 98. Allen DB, Meltzer EO, Lemanske RF, Phil- antihistamines: celebrating a century of of seasonal allergic rhinitis. J Allergy Clin pot EE, Faris MA, Kral KM et al. No progress. J Allergy Clin Immunol growth suppression in children treated with 86. Meltzer E, Kunjibettu S, Hall N, Wingert- the maximum recommended dose of flutica- 75. Church MK, Maurer M, Simons FER, zahn M, Murcia C, Berger W et al. Efficacy sone propionate aqueous nasal spray for Bindslev-Jensen C, Van Cauwenberge P, and safety of ciclesonide, 200 microg once one year. Allergy Asthma Proc Bousquet J et al. Risk of first-generation daily, for the treatment of perennial allergic H1-antihistamines: a GA2LEN position rhinitis. Ann Allergy Asthma Immunol 99. Daley-Yates PT, Kunka RL, Yin Y, paper. Allergy 2010;65:459–466.
Andrews SM, Callejas S, Ng C.
76. Ng KH, Chong D, Wong CK, Ong HT, Lee 87. Berger W, Nayak A, Lanier B, Kaiser H, Bioavailability of fluticasone propionate CY, Lee BW et al. Central nervous system LaForce C, Darken P et al. Efficacy and and mometasone furoate aqueous nasal side effects of first- and second-generation safety of once-daily ciclesonide nasal spray sprays. Eur J Clin Pharmacol antihistamines in school children with peren- in children with allergic rhinitis. Pediatr nial allergic rhinitis: a randomized, double- Asthma Allergy Immunol 2008;21:73–82.
100. Fink RS, Pierre LN, Daley-Yates PT, Rich- blind, placebo-controlled comparative study.
88. Chervinsky P, Kunjibettu S, Miller D, ards DH, Gibson A, Honour JW. Hypo- Prenner B, Raphael G, Hall N et al.
thalamic-pituitary-adrenal axis function 77. Anolik R, Pearlman D, Teper A, Gates D.
Long-term safety and efficacy of intranasal after inhaled corticosteroids: unreliability of Mometasone furoate improves nasal and ciclesonide in adult and adolescent patients urinary free cortisol estimation. J Clin ocular symptoms of seasonal allergic rhini- with perennial allergic rhinitis. Ann Allergy Endocrinol Metab 2002;87:4541–4546.
tis in adolescents. Allergy Asthma Proc Asthma Immunol 2007;99:69–76.
101. Schenkel EJ, Skoner DP, Bronsky EA, 89. Baena C, Patel P. Efficacy and long-term Miller SD, Pearlman DS, Rooklin A et al.
78. Ratner P, Meltzer E, Teper A. Mometa- safety of mometasone furoate nasal spray Absence of growth retardation in children sone furoate nasal spray is safe and effec- in children with perennial allergic rhinitis.
with perennial allergic rhinitis after one tive for 1-year treatment of children with Curr Med Res Opin 2010;26:2047–2055.
year of treatment with mometasone furoate perennial allergic rhinitis. Int J Pediatr 90. McCormack P, Scott L. Fluticasone furo- aqueous nasal spray. Pediatrics ate: intranasal use in allergic rhinitis. Drugs 79. Wandalsen G, Mendes AI, Sole D. Objec- 102. Rachelefsky GS. Pharmacologic manage- tive improvement in nasal congestion and 91. Mspero J, Rosenblut A, Finn A, Lim J, ment of allergic rhinitis. J Allergy Clin nasal hyperreactivity with use of nasal ste- Wu W, Philpot E. Safety and efficacy of roids in persistent allergic rhinitis. Am J fluticasone furoate in pediatric patients with 103. Skoner DP, Rachelefsky GS, Meltzer EO, Rhinol Allergy 2010;24:e32–e36.
perennial allergic rhinitis. Otolaryngology Chervinsky P, Morris RM, Seltzer JM 80. Nathan R, Berger W, Yang W, Cheema A, – Head and Neck Surgery 2008;138:30–37.
et al. Detection of growth suppression in Silvey M, Wu W et al. Effect of once-daily 92. Al S, Fedorowicz Z, Alhashimi D, Jamal children during treatment with intranasal fluticasone furoate nasal spray on nasal A. Topical nasal steroids for intermittent beclomethasone dipropionate. Pediatrics symptoms in adults and adolescents with and persistent allergic rhinitis in children.
perennial allergic rhinitis. Ann Allergy Cochrane Database Syst Rev 104. Mygind N, Laursen LC, Dahl M. Systemic Asthma Immunol 2008;100:497–505.
corticosteroid treatment for seasonal aller- 81. Jacobs R, Martin B, Hampel F, Toler W, 93. Meltzer E, Tripathy I, Maspero J, Wu W, gic rhinitis: a common but poorly docu- Ellsworth A, Philpot E. Effectiveness of Philpot E. Safety and tolerability of flutica- mented therapy. Allergy 2000;55:11–15.
fluticasone furoate 110 mug once daily in the sone furoate nasal spray once daily in pae- 105. Wolthers OD, Pedersen S. Short-term treatment of nasal and ocular symptoms of diatric patients aged 6–11 years with growth in children with allergic rhinitis seasonal allergic rhinitis in adults and ado- allergic rhinitis: subanalysis of three ran- treated with oral antihistamine, depot and lescents sensitized to mountain cedar pollen.
domized, double-blind, placebo-controlled, intranasal glucocorticosteroids. Acta Paedi- Curr Med Res Opin 2009;25:1393–1401.
multicentre studies. Clin Drug Invest 82. Vasar M, Houle P, Douglass J, Meltzer E, 106. LiAlbert M, Abdullah V, Tsen C, Au C, Silvey M, Wu W et al. Fluticasone furoate 94. Camargos P, Ibiapina C, Lasmar L, Cruz Lam H, So H et al. Leukotriene receptor nasal spray: effective monotherapy for AA. Obtaining concomitant control of antagonist in the treatment of childhood symptoms of perennial allergic rhinitis in allergic rhinitis and asthma with a nasally allergic rhinitis – a randomized placebo- adults/adolescents. Allergy Asthma Proc inhaled corticosteroid. Allergy controlled study. Pediatr Pulmonol 83. Fokkens WJ, Jogi R, Reinartz S, Sidorenko 95. Pedersen W, Hjuler I, Bisgaard H, Mygind 107. Razi C, Bakirtas A, Harmanci K, Turktas I, Sitkauskiene B, Faris MA et al. Once N. Nasal inhalation of budesonide from a I, Erbas D. Effect of montelukast on symp- daily fluticasone furoate nasal spray is spacer in children with perennial rhinitis toms and exhaled nitric oxide levels in 7- to effective in seasonal allergic rhinitis caused and asthma. Allergy 1998;53:383–387.
14-year-old children with seasonal allergic by grass pollen. Allergy 2007;62:1078–1084.
96. Lohia S, Schlosser RJ, Soler ZM. Impact rhinitis. Ann Allergy Asthma Immunol 84. Martin B, Ratner P, Hampel F, Andrews of intranasal corticosteroids on asthma out- C, Toler T, Wu W et al. Optimal dose comes in allergic rhinitis: a meta-analysis.
108. Wilson AM, O'Byrne PM, Parameswaran K.
selection of fluticasone furoate nasal spray Leukotriene receptor antagonists for allergic 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd Paediatric rhinitis Roberts et al.
rhinitis: a systematic review and meta-analy- controlled trial comparing fluticasone aque- 132. Kopp MV. Role of immunmodulators in sis. Am J Med 2004;116:338–344.
ous nasal spray in mono-therapy, fluticasone allergen-specific immunotherapy. Allergy 109. Grainger J, Drake-Lee A. Montelukast in plus cetirizine, fluticasone plus montelukast allergic rhinitis: a systematic review and and cetirizine plus montelukast for seasonal 133. Durham SR, Walker SM, Varga EM, meta-analysis. Clin Otolaryngol allergic rhinitis. Clin Exp Allergy 2004;34: Jacobson MR, O'Brien F, Noble W et al.
Long-term clinical efficacy of grass pollen 110. Pattanaik D, Lieberman P. Vasomotor 121. Watanasomsiri A, Poachanukoon O, Vich- immunotherapy. N Engl J Med rhinitis. Curr Allergy Asthma Rep yanond P. Efficacy of montelukast and loratadine as treatment for allergic rhinitis 134. Radulovic S, Wilson D, Calderon M, Dur- 111. Meltzer EO, Caballero F, Fromer LM, in children. Asian Pac J Allergy Immunol ham S. Systematic reviews of sublingual Krouse JH, Scadding G. Treatment of immunotherapy (SLIT). Allergy congestion in upper respiratory diseases.
122. Chen S, Lu K, Sun H, Chang W, Lue K, Int J Gen Med 2010;3:69–91.
Chou M. Randomized placebo-controlled 135. Pajno GB, Caminiti L, Crisafulli G, Vita 112. Schuller DE, Selcow JE, Joos TH, Hann- trial comparing montelukast and cetirizine D, Valenzise M, De Luca R et al. Direct away PJ, Hirsch SR, Schwartz HJ et al. A for treating perennial allergic rhinitis in comparison between continuous and multicenter trial of nedocromil sodium, 1% children aged 2–6 yr. Pediatr Allergy Immu- coseasonal regimen for sublingual nasal solution, compared with cromolyn immunotherapy in children with grass sodium and placebo in ragweed seasonal 123. Blom HM, Van Rijswijk JB, Garrelds IM, allergy: a randomized controlled study.
allergic rhinitis. J Allergy Clin Immunol Mulder PG, Timmermans T, Gerth van Pediatr Allergy Immunol Wijk R. Intranasal capsaicin is efficacious 113. Garavello W, Di B, Romagnoli M, Sam- in non-allergic, non-infectious perennial rhi- 136. Novembre E, Galli E, Landi F, Caffarelli bataro G, Gaini R. Nasal rinsing with nitis. A placebo-controlled study. Clin Exp C, Pifferi M, De Marco E et al. Coseasonal hypertonic solution: an adjunctive treat- sublingual immunotherapy reduces the ment for pediatric seasonal allergic rhino- 124. Calderon MA, Gerth van Wijk R, Eichler development of asthma in children with conjunctivitis. Int Arch Allergy Immunol I, Matricardi PM, Varga EM, Kopp MV allergic rhinoconjunctivitis. J Allergy Clin et al. Perspectives on allergen-specific 114. Li H, Sha Q, Zuo K, Jiang H, Cheng L, immunotherapy in childhood: an EAACI 137. Valovirta E, Berstad AKH, de Blic J, Bufe Shi J et al. Nasal saline irrigation facilitates position statement. Pediatr Allergy Immunol A, Eng P, Halken S et al. Design and control of allergic rhinitis by topical steroid recruitment for the GAP trial, investigating in children. ORL J Otorhinolaryngol Relat 125. Bufe A, Roberts G. Specific immunother- the preventive effect on asthma apy in children. Clin Exp Allergy development of an SQ-standardized grass 115. Jeffe JS, Bhushan B, Schroeder J. Nasal allergy immunotherapy tablet in children saline irrigation in children: a study of 126. Walker SM, Durham SR, Till SJ, Roberts with grass Pollen–Induced allergic compliance and tolerance. Int J Pediatr G, Corrigan CJ, Leech SC et al. Immuno- rhinoconjunctivitis. Clin Ther therapy for allergic rhinitis. Clin Exp 116. Vignola AM, Humbert M, Bousquet J, 138. Wahn U, Tabar A, Kuna P, Halken S, Boulet LP, Hedgecock S, Blogg M et al.
127. Halken S, Lau S, Valovirta E. New visions Montagut A, de Beaumont O et al. Efficacy Efficacy and tolerability of anti-immuno- in specific immunotherapy in children: an and safety of 5-grass-pollen sublingual globulin E therapy with omalizumab in iPAC summary and future trends. Pediatr immunotherapy tablets in pediatric allergic patients with concomitant allergic asthma Allergy Immunol 2008;19(Suppl 70):60–70.
rhinoconjunctivitis. J Allergy Clin Immunol and persistent allergic rhinitis: SOLAR.
128. Calderon MA, Alves B, Jacobson M, Hur- witz B, Sheikh A, Durham S. Allergen 139. Bufe A, Eberle P, Franke B, Funck J, Kim- 117. Man LX. Complementary and alternative injection immunotherapy for seasonal aller- mig M, Klimek L et al. Safety and efficacy medicine for allergic rhinitis. Current gic rhinitis. Cochrane Database Syst Rev in children of an SQ-standardized grass Opinion in Otolaryngology & Head & Neck 2007 (1):CD001936.
allergen tablet for sublingual immunother- 129. Vance GHS, Goldring S, Warner JO, Cox apy. J Allergy Clin Immunol 118. Anolik R, Mometasone Furoate Nasal H, Sihra B, Hughes S et al. A national Spray With Loratadine Study Group. Clini- audit of pollen immunotherapy for children 140. Penagos M, Compalati E, Tarantini F, cal benefits of combination treatment with in the United Kingdom: patient selection Baena C, Huerta J, Passalacqua G et al.
mometasone furoate nasal spray and lorat- and programme safety. Clin Exp Allergy Efficacy of sublingual immunotherapy in adine vs monotherapy with mometasone the treatment of allergic rhinitis in pediatric furoate in the treatment of seasonal allergic 130. Niggemann B, Jacobsen L, Dreborg S, patients 3 to 18 years of age: a meta-analy- rhinitis. Ann Allergy Asthma Immunol Ferdousi HA, Halken S, Koivikko A et al.
sis of randomized, placebo-controlled, Five-year follow-up on the PAT study: spe- double-blind trials. Ann Allergy Asthma 119. Martin BG, Andrews CP, van Bavel JH, cific immunotherapy and long- term pre- Hampel FC, Klein KC, Prillaman BA et al.
vention of asthma in children. Allergy 141. Fiocchi A, Pajno G, La G, Pezzuto F, Comparison of fluticasone propionate Incorvaia C, Sensi L et al. Safety of sublin- aqueous nasal spray and oral montelukast 131. Portnoy J, Bagstad K, Kanarek H, Pacheco gual-swallow immunotherapy in children for the treatment of seasonal allergic rhini- F, Hall B, Barnes C. Premedication reduces aged 3 to 7 years. Ann Allergy Asthma tis symptoms. Ann Allergy Asthma Immunol the incidence of systemic reactions during inhalant rush immunotherapy with mixtures 142. Calderon MA, Simons FER, Malling HJ, 120. Di LG, Pacor ML, Pellitteri ME, Morici G, of allergenic extracts. Ann Allergy Asthma Lockey RF, Moingeon P, Demoly P. Sub- Di GA, Lo BC et al. Randomized placebo- lingual allergen immunotherapy: mode of 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd Roberts et al.
Paediatric rhinitis action and its relationship with the safety immunotherapy tablet. J Allergy Clin large-scale, retrospective, matched cohort profile. Allergy 2012;67:302–311.
study. Ann Allergy Asthma Immunol 143. Senna G, Lombardi C, Canonica GW, 146. Schadlich PK, Brecht JG. Economic evalu- Passalacqua G. How adherent to sublin- ation of specific immunotherapy versus 149. Wong IY, Soh SE, Chng SY, Shek LP, gual immunotherapy prescriptions are symptomatic treatment of allergic rhinitis Goh DY, Van Bever HP et al. Compliance patients? The manufacturers' viewpoint in Germany. Pharmacoeconomics with topical nasal medication – an J Allergy Clin Immunol 2010;126: evaluation in children with rhinitis.
147. Hankin C, Cox L, Lang D, Levin A, Gross Pediatr Allergy Immunol 2010;21: 144. Vita D, Caminiti L, Ruggeri P, Pajno GB.
G, Eavy G et al. Allergy immunotherapy Sublingual immunotherapy: adherence among Medicaid-enrolled children with 150. Van Cauwenberge P, Bachert C, based on timing and monitoring control allergic rhinitis: patterns of care, resource Passalacqua G, Bousquet J, Canonica visits. Allergy 2010;65:668–669.
use, and costs. J Allergy Clin Immunol GW, Durham SR et al. Consensus 145. Durham SR, Emminger W, Kapp A, statement on the treatment of allergic Colombo G, de Monchy JG, Rak S et al.
148. Hankin C, Cox L, Lang D, Bronstone A, rhinitis. European Academy of Allergol- Long-term clinical efficacy in grass pollen– Fass P, Leatherman B et al. Allergen ogy and Clinical Immunology. Allergy induced rhinoconjunctivitis after treatment immunotherapy and health care cost with SQ-standardized grass allergy benefits for children with allergic rhinitis: a 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd
S-3 Leitlinie AWMF-Register-Nr. 043/044 Epidemiologie, Diagnostik, Therapie und Mana- gement unkomplizierter bakterieller ambulant erworbener Harnwegsinfektionen bei erwachsenen Patienten Erstellungsdatum: 2010 Nächste Überprüfung geplant: 2015 Kurzfassung 18. März 2010