Allegric Rhinitis: Pearls of Wisdom

This provides an overview of Allergic Rhinitis and its management. It is very useful for students of Rhinology and clinicians managing this disease. It introduces them to a systematic approach of assessing allergic rhinitis patients which is very commonly found in most populations and causes considerably morbidity. Allergy per se is a very difficult subject to master and it is with great perseverance one can treat patients suffering from this condition. The cornerstone of managing a patient of allergic rhinitis is first and foremost obtaining a good history. This is to be followed by a thorough examination and investigations. The general practitioner is the first expert to be involved in management of allergic rhinitis patient followed by specialists otorhinolaryngologists, and finally by allied healthcare personnel. Inflammation of nose and paranasal sinuses are characterized by two or more symptoms-namely, either nasal blockage; obstruction; congestion or nasal discharge. Associated symptoms include facial pain; pressure and either reduction or loss of smell. Certain diagnostic endoscopic signs of nasal polyps and or mucopurulent discharge and or mucosal oedema in the middle meatus and or CT changes of mucosa within the ostoemeatal complex, and or sinuses are seen. Definitions, aetiologies, clinical presentations, diagnosis; prognosis and management of allergic rhinitis is dealt with. Common allergens causing the disease are mentioned, pathophysiology and classification of allergic rhinitis is discussed in detail. Different types of allergen testing are highlighted along with their specific role and uniqueness. Principles of immunotherapy in treatment of allergic rhinitis are discussed here. Health effects of allergic rhinitis along with its impact on physical quality of life is mentioned. The basic idea of this presentation is to improve diagnostic accuracy by promoting appropriate use of ancillary tests like nasoendoscopy, allergy testing, computed tomography etc. and reduce inappropriate antibiotic use. The basic treatment plan of allergic rhinitis is according to the severity and duration. It consists of allergen avoidance, pharmacotherapy, allergen immunotherapy and surgery which has limited role.


Introduction
lining contains secretion of IgA, proteins and enzymes. Nasal cilia propel the matter towards the natural ostia at frequency of 10-15 beats; min. Mucous moves at a rate of 2.5 -7.5ml. per min ( Figure  1). Rhinitis is the presentation of two or more nasal symptoms for more than one a day namely Nasal congestion; obstruction, Rhinorrhea, Sneezing, Itching, Impairment of smell. Rhinitis occurs most commonly as Allergic Rhinitis. Non-infectious rhinitis has been classified as either Allergic or Non-Allergic Rhinitis. Allergic Rhinitis affects 15-30% of population with a wide geographic variance. It is more common in children & adolescents. 50% of all rhinitis in E.N.T. Clinics is Allergic Rhinitis. Allergic Rhinitis is defined as immunologic nasal response, primarily mediated by IgE. Non-Allergic Rhinitis is defined as rhinitis symptoms in the absence of identifiable allergy, structural abnormality or sinus disease. So, Allergic Rhinitis is an inflammation of the nasal mucosa, caused by allergen. It is the most common Atopic allergic reaction.   Figure 2). Rhinitis is the presentation of two or more nasal symptoms for more than one a day namely Nasal congestion; obstruction, Rhinorrhea, Sneezing, Itching, Impairment of smell. Rhinitis occurs most commonly as Allergic Rhinitis. Non-infectious rhinitis has been classified as either Allergic or Non-Allergic Rhinitis. Allergic Rhinitis affects 15-30% of population with a wide geographic variance. It is more common in children & adolescents. 50% of all rhinitis in E.N.T. Clinics is Allergic Rhinitis [3]. Allergic Rhinitis is defined as immunologic nasal response, primarily mediated by IgE. Non-Allergic Rhinitis is defined as rhinitis symptoms in the absence of identifiable allergy, structural abnormality or sinus disease. So, Allergic Rhinitis is an inflammation of the nasal mucosa, caused by allergen. It is the most common Atopic allergic reaction.

Pathophysiology
Immunoglobulin IgE mediated type 1 hypersensitivity response to an antigen (allergen) in a genetically susceptible person. IgE is produced from plasma cells & the process is regulated by T-Suppressor lymphocytes or T-helper cells. IgE has affinity for mast cells & basophils and gets fixed to the surface of mast cells by its Fc end. Type 1 Hypersensitivity causes local vasodilation & increased capillary permeability. There is edema of the submucosal tissue by allergic fluid followed by infiltration by eosinophils and plasma cells leading to vascular dilatation which causes engorgement of the inferior turbinates and there is increased activity of seromucinous glands [4]. Histamine exerts its pharmacologic effect on smooth muscle, vascular endothelium & mucous glands. Number of IgE molecules has been estimated as 5300 to 27,000 in non-allergic subject & 15,000 to 41,000 in allergic subjects. Hypersensitivity of the host depends on antigen dose, frequency of exposure, genetic make-up, and hormone activity of the body.

Classification
Allergic Rhinitis is currently classified into intermittent and persistent. In intermittent AR the symptoms are present less than 4 days per week and less than 4 weeks per year [5]. In persistent AR the symptoms are present for greater than 4 days per week and for greater than 4 weeks per year. The severity of AR is classified into mild and moderate to severe. Mild AR doesn't interfere with daily activities or doesn't produce any troublesome symptoms. Moderate to severe AR interferes at least with one of the factors such as impaired sleep, hampered daily activities/work, school/ sick absenteeism, also produces troublesome symptoms. AR is formerly classified into seasonal and perennial based on the allergens. Seasonal Hay Fever, misnomer-no hay/no fever. Summer Cold caused by viruses causing URTI. Rose Fever seen usually in Indian Subcontinent (colorful/fragrant flowering plants). Perennial Allergens present throughout the year.

Investigations
Skin prick tests---gold standard. This is also known as Scratch Test; Intradermal Test. Controlled amounts of allergen & control substances are introduced into the skin this procedure is convenient, safe & widely accepted (Figure 4). Goal of the investigation is the detection of immediate allergic response caused by release of mast cells or basophil IgE specific mediators Wheal; Flare after 15 mins [6]. More investigations are such as RAST-Radio-Allergo-Sorbent Test for specific IgE estimation. PRIST-Plasma Reactive Immuno-Sorbent Test for specific IgE estimation. SET Test-Skin End-Point Titration Test Latest skin test for allergy & is more reliable. Less common tests are total serum IgE, total blood eosinophil count, nasal smears may show increased eosinophilic level, PATCH TEST is used to determine delayed type hypersensitivity & the allergen is placed in the skin for 48hrs [7]. The area of reaction is noted and if any allergens present are identified. This is more useful in skin problems & food allergy.  The potential allergen is sprayed into the nose & the number of SNEEZES counted or any change in Rhinomanometry is noted. Very time-consuming test as each allergen takes 20 mins. To test in order to allow the nose to return to normal after the challenge. It is useful for rare & occupational allergens. Contraindications of NPT are Pregnancy; < 5yrs. age; Recent nasal surgery <8 wks; Uncontrolled asthma, Nasal; systemic corticosteroids should be avoided for 1wk & Antihistaminics for 72hrs ( Figure 5).

Exhaled Nitric Oxide (E No):
Like e NO in asthma, n NO is a noninvasive marker. Potentially suitable to monitor upper airway inflammation following allergen-induced late response. In AR pts., increased levels of n NO have been measured. However, the applicability of n NO as a marker of upper airway inflammation awaits validation. Exhaled nitric oxide (e NO) is currently the MOST RELIABLE MARKER of rhino-bronchial inflammation, but its routine assessment is difficult as the test is available only in highly specialized centers.

Prognosis
Treatment is available & pts. remain asymptomatic only until re-exposure to allergic antigen. There is no evidence of mortality from the disease but there is very high morbidity. PQLI is affected. Seasonal allergic symptoms improve as patients age.

Management of AR
Management of Allergic Rhinitis includes Allergen avoidance & environmental control measures, Medical; pharmacologic treatment, Immunotherapy and Surgery [8]. Choice of treatment will depend on efficacy, safety, cost-effectiveness, patient preferences, combination, objectives of treatment, likely adherence to recommendations, severity & control of disease and presence of co-morbidities. Practical allergen avoidance tips given by WAO for public education purposes are as follows in (Figure 7).
Non-sedating antihistaminics (Cetirizine; Loratadine) has fewer side effects. Fexofenadine is more effective (has a lower risk of cardiac arrythmias). Decongestants will Shrink mucous membranes by vasoconstriction. These are available OTC; in combination with antihistaminic, analgesics & anti cholinergic [9]. Anticholinergic Agents Inhibit mucous secretions which acts as drying agents. Topical Eye Preparations reduces inflammation; relieves burning and itching (Figure 8).

Immunotherapy (AIT)
SCIT is effective in seasonal pollinosis & mite allergy. SLIT is Effective & safe alternative, best in seasonal AR. COCHRANE reviews shows that both are equally effective & the patient is in equipoise. These are more effective in adult pts. 3yrs. Of treatment with both SCIT & SLIT has been shown to provide long term clinical benefits for at least 2 yrs. after their discontinuation. The choice of therapy depends on grounds of convenience, availability of resources & personal preferences. SCIT requires administration in a specialist clinic whereas SLIT can be self-administered.
Therapeutic formulations, Efficacy criteria. There is ample scope for physicians, patient organizations, companies & regulators to improve clinical trials in AIT and, to provide patients with better treatments. Inclusion of allergic pts. with relevant diseases(s) in AIT trials. Exclusion of polyallergic pts. (with clinically relevant, overlapping allergen exposures) in AIT trials. Clinically defined responders in AIT trials. Allergen exposure chambers in AIT trials. Differences in regional & seasonal exposures. Adaptive trial designs should be discussed with regulatory bodies. Patient-to-patient differences in treatment adherence & allergen exposure. (Use of "e-health" is recommended). The placebo effect in AIT is to be considered. Ethical & technical aspects of DBPC; RCT's, especially in paediatric populations. The importance of safety reporting. (WAO guidelines for reporting systemic & local adverse events should be applied). h) How quickly can one expect to get relief from allergy treatment?

Omalizumab for Treatment of AR
i) Taking corticosteroids inhalers to control asthma symptoms, can one also take allergy medications? j) What are the types of allergy tests? IgE skin test; Intradermal test; Specific IgE in blood.