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Consensus Statement* on the Treatment of Allergic Rhinitis

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Consensus Statement* on the Treatment of Allergic Rhinitis Allergy 2000: 55: 116±134 Copyright # Munksgaard 2000 Printed in UK. All rights reserved ALLERGY ISSN 0105-4538 Position paper Consensus statement* on the treatment of allergic rhinitis P. van Cauwenberge (Belgium) C. Bachert (Belgium) G. Passalacqua (Italy) J. Bousquet (France) G. W. Canonica (Italy) S. R. Durham (UK) W. J. Fokkens (Netherlands) P. H. Howarth (UK) V. Lund (UK) H.-J. Malling (Denmark) N. Mygind (Denmark) D. Passali (Italy) G. K. Scadding (UK) D.-Y. Wang (Singapore) Department of Otorhinolaryngology, Ghent University Hospital, De Pintelaan 185, B-9000 Ghent, Belgium Prof. P. van Cauwenberge Department of Otorhinolaryngology Ghent University Hospital De Pintelaan 185 B-9000 Ghent Belgium Accepted for publication 12 October 1999 variety of pollen allergens including grasses, Parietaria, 1. Introduction Ambrosia, Artemisia, birch, olive, hazelnut, and cypress. Allergic rhinitis (AR) is a high-prevalence disease in The morbidity of SAR obviously depends on the many developed countries, affecting about 10±20% of geographic region, the pollen season of the plants, and the general population (1±5). Several studies based on the local climate. questionnaire and objective testing or medical exam- Several other conditions can cause similar symptoms ination indicate an increasing prevalence of AR in and are referred to as nonallergic (noninfectious) European countries over the last decades (6, 7). rhinitis: NARES (nonallergic rhinitis with eosinophilia AR is characterized by nasal itching, sneezing, watery syndrome); aspirin sensitivity; endocrine, occupational, rhinorrhoea, and nasal obstruction. Additional symp- postinfectious, and side-effects of systemic drugs; abuse toms such as headache, impaired smell, and conjunc- of topical decongestants (rhinitis medicamentosa); and tival symptoms can be associated. According to the time idiopathic rhinitis. Furthermore, diseases such as nasal of exposure, AR can be subdivided into perennial, polyposis, chronic sinusitis, cystic ®brosis, Wegener's seasonal, and occupational disease. Perennial AR disease, benign or malignant tumours, etc. have to be (PAR) is most frequently caused by dust mites and excluded carefully. Therefore, current guidelines (4) animal dander. Seasonal AR (SAR) is related to a wide emphasize the importance of an accurate diagnosis of patients presenting with rhinitis symptoms. In fact, *European Academy of Allergology and Clinical Immunology. several causes may commonly coexist in the same 116 Consensus statement patient, requiring separate consideration. The diagnosis In recent years, new information on the patho- of allergic rhinitis is frequently straightforward, but physiologic mechanisms underlying allergic in¯amma- may also be very complex and dif®cult. The mainstay is tion has accumulated. Based on these recent data, the an accurate history including an allergy history, based therapeutic strategies have been partly modi®ed or on familial and personal history, recent clinical aspects, improved, and new drugs or new routes of administra- and prior treatment. The possible presence of lower tion, dosages, and schedules have been studied and respiratory tract disease, skin symptoms, or pollen- validated. Intended for the specialist as well as the related food allergies should always be investigated, general practitioner, this paper presents the state of the since they are commonly associated with rhinitis. This is art of AR treatment, and provides a well-documented followed by a clinical examination of the nose. A major review of the drugs available and their place in the advance has been the introduction of rigid and ¯exible management of the disease. nasal endoscopes and, if sinusitis is considered, the availability of CT scanning. When an allergic pathogenesis of the disease is suspected, the skin prick test (SPT) with standardized 2. Mechanisms of AR allergens should be performed. The measurement of AR results from IgE-mediated allergy, associated with allergen-speci®c IgE in serum (as single allergens or cellular in¯ammation of the nasal mucosa of variable groups) is a useful diagnostic approach in selected cases intensity. The mechanisms of AR have been largely (skin test with dif®cult interpretation or not feasible, clari®ed within the last 15 years from studies in children, allergen not available for SPT, etc.). As naturally occurring disease and by the use of nasal sensitization to an allergen does not necessarily mean challenge models in which cell in®ltration and cell that the individual patient suffers from clinical disease, activation have been assessed (15±18). These studies the clinical relevance of skin or speci®c IgE results highlight the presence of eosinophilic airway in¯amma- should be demonstrated before introducing therapies tion and identify the enhanced expression of endothelial such as immunotherapy or environmental control. and epithelial adhesion molecules (19, 20), as well Whereas the clinical relevance in SAR usually can be as chemokines and cytokines (21, 22). The release demonstrated by carefully analysing patient history, of mediators from in®ltrating leukocytes as well as nasal allergen challenge tests may be useful in PAR. resident tissue cells, such as mast cells, is implicated in Allergen-speci®c diagnosis (as well as therapy) should both the symptoms and the development of nasal be based on puri®ed standardized allergen extracts. nonspeci®c hyperreactivity. AR appears to impose variable restrictions on the Histamine appears to be a major mediator released physical, psychologic, and social aspects of patients' by mast cells in seasonal and perennial allergen lives, and may have an impact on their careers. AR is exposure (23), but other mediators such as leukotrienes, underestimated as a cause of suffering and impaired prostaglandins, and kinins may also contribute to the quality of life (8±10). If symptoms of AR are not well symptomatology through their interaction with neural controlled, they may contribute to learning problems and vascular receptors (24, 25). In addition to these and sleep disturbances (11, 12). events, there is also neural involvement in the disease, For AR, direct yearly costs are estimated at 1.0±1.5 with neuropeptide release from cholinergic and pepti- billion Euro, while indirect costs are estimated at dergic nerves. Some different aspects of the two forms 1.5±2.0 billion Euro in Europe (13). Finally, the possible of AR are summarized in Table 1. association between AR and other conditions including The enhanced expression of TH2-like cytokines, such asthma, sinusitis, otitis media, nasal polyposis, lower as interleukin (IL)-4 and IL-5, within the nasal mucosa, respiratory tract infection, and even dental mal- generated by T cells, as well as mast cells, is a hallmark occlusion should be considered in evaluating the of AR and is relevant to the selective recruitment and socio-economic impact of the disease (14). survival of eosinophils (26, 27). The local generation of cytokines such as IL-5 and GM-CSF by eosinophils Table 1. Characteristics of allergic rhinitis themselves, along with the generation of cytokines and Characteristic Seasonal Perennial chemokines by the epithelium, leads to the persistence of the eosinophil within the tissue. The epithelium is Obstruction Variable Always, predominant Secretion Watery, common Seromucous, postnasal increasingly recognized as an active cell population, drip, variable providing cytokines and chemokines relevant to the Sneezing Always Variable local tissue cell recruitment (28), with an accumulation Smell disturbance Variable Common of mast cells, basophils, eosinophils, and T cells evident Eye symptoms Common Rare at this location in AR. Once induced, this in¯ammatory Asthma Variable Common Chronic sinusitis Occasional Frequent process within the nasal mucosa persists for several weeks after allergen exposure (29). In cases of PAR 117 van Cauwenberge et al. where there is continuous low-dose allergen exposure, cat allergens. Although frequent washing of cats there is persistent nasal mucosal in¯ammation (30). reduces allergen recovery in the lavage (43), clinical The concept that the mechanisms of disease genera- studies have not shown clear bene®t from this tion provide a framework for rational therapy in this procedure when carried out once a week (44). If disorder is based on the complex in¯ammatory reaction removal of the cat is not acceptable to the patient, the rather than on the symptoms alone. pet should at least be excluded from the bedroom or kept outdoors. Avoidance of pollen is often impossible due to its ubiquitous nature. 3. Allergen avoidance The triggering event of AR is the contact of the 4. Oral antihistamines responsible allergen with the nasal mucosa. This event, mainly through the degranulation of mast cells, leads to General aspects the clinical early-phase response and initiates the Histamine is a major mediator involved in the subsequent allergic in¯ammatory process. The severity development of AR symptoms: the increase of hista- of the disease and its natural course correlate well with mine concentration in nasal secretions of atopic patients the allergen concentration in the environment (31±33). after nasal allergen challenge and during natural Thus, the ®rst therapeutic approach to the control of allergen exposure has been clearly demonstrated (45, symptoms is prevention, by identi®cation and avoid- 46). The role of histamine in the nasal allergic reaction ance of the causal allergen(s) (4, 34). The removal of the is also
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