Allergic Rhinitis-Management Strategies and Review of Recent Indian Guidelines

Allergic Rhinitis is widely recognized as the most common allergic disease, is an allergen-induced upper-airway inflammatory disease characterized by hyperactive airway mucosa, which leads to rhinorrhea, sneezing, nasal pruritus, and congestion, as well as red, itchy, watery eyes, itching of the palate and throat, and cough. (1) The prevalence of allergic rhinitis has gradually risen in India in the last 2 decades. Allergic rhinitis and asthma coexist in 70–80% of Indian patients adding to the disease burden. (2)

Allergic Rhinitis (AR) and Asthma: Need for a Unified Approach:

AR was traditionally considered a localized condition of the nose and nasal passages. However, current clinical evidence suggests that AR may develop as part of systemic airway disease, affecting the entire respiratory tract. Over the years, studies have shown that an allergen triggering the upper airways, also causes a local inflammatory response and an inflammatory process in the lower airways, explaining the coexistence of rhinitis with asthma. In India, AR affects up to 30% of the population, and 15% eventually develop asthma, necessitating AR to be considered a systemic disease rather than a local one. (3, 4) Despite multiple therapeutic options available, AR management in India remains sub-optimal, owing to the unaffordability of inhaled and intranasal corticosteroids and the deprivation of advanced immunomodulatory biologic therapies. (5)

To optimize care in managing AR and its related co-morbidities, the Association of Otolaryngologists of India (AOI) has put forth a consensus expert document elaborating on guidelines for the integrated care of AR patients in India. (6) This article summarizes the clinical aspects of these recommendations- diagnosis and management of AR; and sheds light on the scope and studies supporting the role of Montelukast in successfully managing the disease.

Analyzing the AOI Guidelines: Steps towards Diagnosis and management-

Taking real-world evidence into consideration, the Association of Otolaryngologists of India (AOI) has put forth practice-oriented guidelines providing specific recommendations for the choice of treatment and the rationale behind it, which is best suited for an individual patient. (6) This ensures a systematic and stepwise diagnostic work-up, with clinically relevant treatment decisions

Patient Profile with the identification of common signs and symptoms of allergic rhinitis is the primary step for initiating appropriate treatment.

• Sneezing, rhinorrhea (runny nose), nasal congestion, and itching are common symptoms of rhinitis. Moreover, itchy nose, itching palate, and eye involvement are other symptoms of AR.
• Extra nasal symptoms involving intense itching, redness, and swelling of the eye's conjunctiva with lacrimation, eyelid swelling, and periorbital edema(in severe cases), need to be assessed.
• Clinical tests to diagnose AR with asthma involve allergic testing using a skin prick test, IgE estimation, and lung function tests.

Diagnostic Protocols

• A comprehensive assessment of history, and physical and clinical examination constitute the foundation for establishing an AR diagnosis.
• Differential diagnoses of diseases with overlapping symptoms are a priority, and they should be ruled out to direct appropriate treatment toward AR.
• The cornerstones of a clinically successful intervention strategy involve effective control measures and identifying patients who may benefit from early intervention in the natural history of the disease.

Treatment of AR:

• The primary objective of treatment for allergic rhinitis is symptom alleviation and the avoidance of disease progression. AR pharmacotherapy should be based on the disease severity and associated co-morbidities, efficacy of the drugs, affordability, and availability.
• In the case of mild, intermittent, and seasonal AR, antihistamines are the first-line therapy. Antihistamines have limited usage in specific patient categories like infants below six months and pregnant women. Diagnosis must be re-considered if AR symptoms are not controlled within 1-2 weeks.
• In persistent AR with moderate-to-severe symptoms, intranasal corticosteroids (INCS), used alone or in conjunction with antihistamines, constitute the backbone of AR treatment.
• Oral and intranasal decongestants help relieve nasal congestion in patients with allergic rhinitis, but caution should be exercised for pregnant women, uncontrolled hypertensives, and severe coronary artery disease patients.

Scope of Leukotriene Receptor Antagonists (LTRAs) in managing AR

• In AR patients with concomitant asthma, Leukotriene Receptor Antagonists (LTRAs) are valuable for reducing bronchospasm and attenuating the inflammatory response.
• In case of lack of efficacy or tolerability issues of oral antihistamines and intranasal corticosteroids, LTRAs are to be considered. Montelukast, a widely used LTRA, is recommended for not more than six weeks.
• Patients with AR who have concomitant asthma, especially exercise-induced and aspirin-exacerbated respiratory disease, might benefit from an LTRA more than from an oral antihistamine.

Position of Montelukast in AR- Study testimonials-

• Montelukast is a selective and orally active LTRA that blocks the cysteinyl leukotriene 1 (CysLT1) receptor (7). Given the involvement of CysLTs in inflammatory processes in AR, the potency of Montelukast directly results from its anti-inflammatory actions. Its main effect in AR is summarized below.

Managing night-time AR symptoms-Nasal obstruction, a leukotriene-mediated effect is reported in 80% of patients with allergic rhinitis. Night-time nasal blockage often does not respond to antihistamines / INCS, unlike Montelukast, which directly acts on the leukotriene receptors. (8)

• Research now highlights that Montelukast may be used as first-line therapy (alternative to oral Antihistamines) in allergic rhinitis for patients with predominant night-time symptoms. (8)
• Malmstrom et al. conducted a large-scale, double-blind, randomized, placebo-controlled study to evaluate the effects of Montelukast on symptoms of seasonal AR. The results indicated that the drug significantly improved the daytime and nighttime nasal symptoms and improved the composite AR symptoms drastically. (7)
• Results of another study revealed that concurrent LTRA plus antihistamine therapy provide additive benefits for patients with AR, with marked improvements in daytime nasal and eye symptoms, nasal congestion upon awakening, and nighttime sleep quality. (7)

Managing AR -Asthma Co-morbid States

• Studies confirm that adult and pediatric asthma patients with active AR are more likely to require frequent rescue drugs and emergency hospitalizations, emphasizing the fact that optimum control of asthma in AR patients is a necessity to improve prognosis. (9)
• Cysteinyl-leukotrienes (CysLTs) are endogenous inflammatory mediators that play an essential role in allergic airway disease by stimulating bronchoconstriction, mucus production, mucosal edema, and inflammation. Montelukast inhibits these actions by blocking type 1 CysLT receptors found on immunocytes, smooth muscle, and endothelial cells in the respiratory mucosa. Initially developed as a treatment for asthma, Montelukast currently is a widely tested and clinically utilized agent that works in AR -comorbid asthma patients via antagonism of CysLT1Rs. (9)
• Prophylactic Use: Given that CysLTs are important in dendritic cell function, it has been hypothesized that long-term LTRA treatment might give an additional advantage over time by blunting allergic sensitization. Along these lines, a study on patients with seasonal AR highlighted that it is, in fact, beneficial to prescribe Montelukast prophylactically, several weeks before the start of the pollen season. (9)

Safety Profile &Dosage Regime-

Montelukast is a safe and well-tolerated LTRA with mild side effects that generally do not require discontinuation of the drug. (1,9)

Montelukast is available as a 10 mg tablet for use in individuals over the age of 15 years, 5 mg for children aged 6-14 years, and 4 mg for children aged 2-5 years. (1) No dose adjustment is needed in the elderly or those with renal insufficiency. (1) It is available in quick-dissolving granules for use with young children. Its pharmacokinetic characteristics allow for once-daily administration, making it patient-compliant therapy. (1)

Clinical Pointers for Physicians-

• Individuals with AR are at a greater risk of suffering from asthma or developing it later in life.
• Though antihistamines and INCS are pivotal therapeutics in managing AR, they may require complementing support for managing more disturbing nocturnal symptoms and asthma-related complications.
• LTRA monotherapy and concurrent LTRA with antihistamine treatment (combined therapy) help to relieve asthma and AR symptoms.
• Montelukast is an efficacious and well-tolerated prophylactic medication for adults and children with coexisting asthma and allergic rhinitis.
• Backed with demonstrated efficacy and safety, Montelukast oral formulations provide optimum patient convenience, which may yield improved treatment adherence and increased patient satisfaction.