Allergen Patterns in Moderate to Severe Allergic Rhinitis: Indian Observations and Therapeutic Utility of Fexofenadine

Allergic diseases are a major public health concern globally including in India with more than 25% of the population being sensitized to varied allergens. Immense variations in climate, flora, and food habits are responsible for the allergen repertoire of this subcontinent. Pollen, fungal spores, food and insect allergens; and dust mites are some of the predominant allergen sources in South Asia. These allergens can present with diverse clinical manifestations, ranging from mild symptoms to life-threatening conditions. Some of India's common allergic disease conditions include bronchial asthma, atopic rhinitis, allergic dermatitis, urticaria; oral, ocular, and gastrointestinal allergies (1).

Prevalence of Allergic Rhinitis (AR) in India:

The Indian Study on the Epidemiology of Asthma, Respiratory Symptoms, and Chronic Bronchitis (INSEARCH) has reported that out of 20-30% of the clinically diagnosed allergic population, 3.3% are found to be suffering from AR in India. The Asthma Epidemiology Study Group of the Indian Council of Medical Research found the prevalence of AR to be approximately 20% of the population in India (1).

Culprits of AR in India: Review of Allergens

The main causative factor for AR in India is the environmental allergens exposed by direct contact, inhalation, or ingestion (2). The research found that particulates from pollen, fungal spores, insect debris, animal dander, dust mites, and food cause AR in India (3). Figure 1 shows the response to a modified skin prick test to common allergens conducted in a study in Central India (2).

Figure 1: Image recreated from Indian J Otolaryngol Head Neck Surg (October 2022) 74(Suppl 2):S888–S893.

Management of AR: Integrated Approach

An integrated approach including patient education, self-monitoring, regular physician visits and avoidance of triggers, along with pharmacotherapy, when indicated, is the motto of AR management (4). Among the diverse medications like antihistamines, corticosteroids, immunotherapies, and various combination therapies fexofenadine is an approved and optimal antihistamine for the management of AR.

Fexofenadine in AR:

Fexofenadine is a U.S. Food and Drug Administration (FDA) approved second-generation antihistamine to treat AR in both children and adults. It acts by selectively antagonizing H1 receptors on cell surfaces of various organs and also inhibits inflammatory mediators. With a low affinity for cholinergic and α-adrenergic receptors and minimal crossing of the blood-brain barrier (BBB), it is one of the least sedating antihistamines used to treat AR (5).

Fexofenadine for AR: Place in Various Guidelines

Various guidelines suggest the use of fexofenadine for AR. These include:

• The American Academy of Allergy, Asthma & Immunology (AAAAI) guidelines suggest fexofenadine as the preferred second-generation antihistamine among various antihistamines (6).
• The British Society for Allergy & Clinical Immunology (BSACI) suggests fexofenadine as first-line therapy for mild-to-moderate intermittent and mild persistent rhinitis, as it is the least sedating oral antihistamine with a wide therapeutic index (7).
• The Association of Otolaryngologists of India put forward fexofenadine as one of the first-line therapies for mild to moderate intermittent and mild persistent AR (8).

Clinical Evidence of Fexofenadine in AR:

Fexofenadine is Considered a Truly Non-Sedating Antihistamine: Latest 2024 Systematic Review:

A systematic review evaluated the non-sedating property of fexofenadine in AR and urticaria. The review included various randomized controlled trials, review articles, systematic reviews, and meta-analyses, together with post-marketing analysis conducted in healthy subjects and patients with allergies to compare the antihistaminic potential or safety of fexofenadine with other antihistamines or placebo using Positron emission tomography (PET) and proportional impairment ratio (PIR) data. The study found that among the various first and second-generation antihistamines, fexofenadine has a high selectivity for peripheral H1-receptors and does not penetrate the BBB due to its affinity for P-glycoprotein (P-gp) which acts as an efflux pump minimizing its impact on the central nervous system. Thus, the study concluded that fexofenadine is clinically effective as well as non-sedating among various antihistamines (9).

Figure 2: Oral anti-histamines: brain H1 receptor occupancy (H1RO %). Recreated from Ansotegui, I. J. et al. (2024). 40(8), pp. 1297–1309. doi: 10.1080/03007995.2024.2378172.

Take-home points:

• AR affects nearly 20% of the Indian population with sensitization to various allergens.
• Pollen, fungal spores, food allergens, insects, dust, dander, and dust mites are the major allergens affecting the Indian population. Direct contact, inhalation, and ingestion are the major routes of spread of AR.
• Fexofenadine is a second-generation antihistamine approved by the US FDA for AR.
• It is safe, effective with high selectivity for peripheral H1 receptors, non-sedating and does not cross the BBB.
• Various guidelines suggest using fexofenadine for AR due to its advantages over the first and other second-generation drugs with similar efficacy and absence of CNS side effects.
• Most recent research emphasizes that fexofenadine could be considered a truly non-sedating antihistamine for the management of AR.

References:

1. Bhattacharya K, Sircar G, Dasgupta A, Gupta Bhattacharya S. Spectrum of Allergens and Allergen Biology in India. Int Arch Allergy Immunol. 2018;177(3):219-237. doi: 10.1159/000490805. Epub 2018 Jul 27. PMID: 30056449.

2. Jain S, Jain A, Gupta SK. Study of Allergen Patterns in Cases of Moderate to Severe Persistent Allergic Rhinitis in Central India. Indian J Otolaryngol Head Neck Surg. 2022 Oct;74(Suppl 2):888-893. doi: 10.1007/s12070-020-01954-2. Epub 2020 Jul 13. PMID: 36452541; PMCID: PMC9702131.

3. Singh AB, Mathur C (2012) An aerobiological perspective in allergy and asthma. Asia Pac Allergy 2(3):210–222.

4. Co-Authors P, Modi N, Deka N, Kumar R. Allergic Rhinitis STANDARD TREATMENT GUIDELINES 2022 Upendra Kinjawadekar IAP President-Elect 2022. Available from: https://iapindia.org/pdf/Ch-014-Allergic-Rhinitis.pdf.

5. Craun KL, Patel P, Schury MP. Fexofenadine. [Updated 2024 Feb 8]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK556104/.

6. Dykewicz M, Wallace D, Amrol D, Baroody F, Bernstein J, Craig T, et al. Rhinitis 2020: A practice parameter update [Internet]. Available from: https://www.aaaai.org/Aaaai/media/MediaLibrary/PDF%20Documents/Practice%20and%20Parameters/Rhinitis-2020-A-practice-parameter-update.pdf

7. Scadding GK, Kariyawasam HH, Scadding G, Mirakian R, Buckley RJ, Dixon T, et al. BSACI guideline for the diagnosis and management of allergic and non-allergic rhinitis (Revised Edition 2017; First edition 2007). Clinical & Experimental Allergy. 2017 Jul;47(7):856–89.

8. Technohub I. AOIHO [Internet]. [cited 2024 Feb 14]. Available from: https://www.aoiho.org/.

9. Ansotegui IJ, Bousquet J, Canonica GW, Demoly P, Gómez RM, Meltzer EO, Murrieta-Aguttes M, Naclerio RM, Rosario Filho N, Scadding GK. Why fexofenadine is considered as a truly non-sedating antihistamine with no brain penetration: a systematic review. Curr Med Res Opin. 2024 Jul 19:1-13. doi: 10.1080/03007995.2024.2378172. Epub ahead of print. PMID: 39028636.