Pathogenetic rationale for pharmacotherapy of allergic diseases in general medical practice

Background. Allergic reactions occupy a special place among the variety of nosological forms encountered in the activities of a general practitioner. In the scientific community, more and more new approaches to the classification of immune-mediated hypersensitivity reactions underlying the development of allergic diseases appear. The identification of 9 hypersensitivity reactions allows us to expand the existing understanding of the pathogenesis of allergic diseases and the contribution of each type of reaction to the mechanism of their development, allowing for a personalized approach to therapy. The aim of this work is to increase awareness of general practitioners about the pathogenetic aspects of allergy and approaches to optimizing pharmacotherapy to achieve better clinical results.

Results. The main goals of therapy for allergic diseases are to achieve control over the disease or reduce the severity of its clinical manifestations, reduce the frequency of exacerbations and the risk of complications, and improve the quality of life of patients. The treatment strategy adheres to the stepwise principle – the appointment of the required volume of pathogenetically substantiated pharmacotherapy based on the initial assessment of the severity of the disease, followed by a step down or up, taking into account the therapeutic response (respectively, step-down or step-up therapy). To achieve the treatment goals, drugs of various pharmacological groups are used, both improving the long-term prognosis of the disease and reducing the severity of its clinical symptoms without positive long-term effects. Despite the various clinical manifestations of the most common allergic/atopic diseases that make up the "atopic triad", they have universal pathogenetic mechanisms largely associated with the second type of immune response. The use of anti-inflammatory drugs, of which glucocorticoids continue to occupy a leading place, is a pathogenetically substantiated basic therapy for these diseases, and the use of dosage forms (inhalation, topical and intranasal), providing maximum concentration in the inflammation site with a low level in the systemic bloodstream, additionally increases the effectiveness, minimizing systemic side effects. At the same time, histamine H1-receptor blockers, often used in clinical practice, have limited application in the therapy of allergic diseases and are used in the therapy of allergic rhinitis, as well as in a number of clinical situations with atopic dermatitis.

Conclusion. The article presents a pathogenetic rationale for the treatment of allergic diseases using bronchial asthma and allergic rhinitis as an example, based on modern data on the types of hypersensitivity reactions.

1. Murphy K., Weaver C. Janeway’s Immunology. Moscow: Logosfera, 2020. 1184 p. (In Russ.)

2. Churilov L. P., Vasilev A. G. Pathophysiology of the immune system. SPb: Foliant, 2014. 664 p. (In Russ.)

3. Jutel M., Agache I., Zemelka-Wiacek M., et al. Nomenclature of allergic diseases and hypersensitivity reactions: Adapted to modern needs: An EAACI position paper. Allergy. 2023; 78 (11): 2851-2874. DOI: 10.1111/all.15889.

4. Cardona V., Ansotegui I. J., Ebisawa M., et al. World allergy organization anaphylaxis guidance 2020. World Allergy Organ J. 2020; 13 (10): 100472. DOI: 10.1016/j.waojou.2020.100472.

5. Ilina N. I. Allergy in Russia today: problems and solutions. Russian Journal of Allergy; 19 (3): 285-288. (In Russ.)

6. Abbas A. K., Lichtman A. H., Pillai S. Basic immunology: Functions and disorders of the immune system, 6e: Sae-E-Book. Elsevier Health Sciences, 2024.

7. Cabeza-Cabrerizo M., Cardoso A., Minutti C. M., et al. Dendritic cells revisited. Annual review of immunology. 2021; 39 (1): 131-166.

8. Balan S., Saxena M., Bhardwaj N. Dendritic cell subsets and locations. Int Rev Cell Mol Biol. 2019; 348: 1-68. DOI: 10.1016/bs.ircmb.2019.07.004. Epub 2019 Sep 3. PMID: 31810551.

9. Jin J., Sunusi S., Lu H. Group 2 innate lymphoid cells (ILC2s) are important in typical type 2 immune-mediated diseases and an essential therapeutic target. J Int Med Res. 2022; 50 (1): 3000605211053156. DOI: 10.1177/03000605211053156. PMID: 35048721; PMCID: PMC8796086.

10. Varricchi G., Bencivenga L., Poto R., et al. The emerging role of T follicular helper (TFH) cells in aging: Influence on the immune frailty. Ageing Res Rev. 2020; 61: 101071. DOI: 10.1016/j.arr.2020.101071. Epub 2020 Apr 25. PMID: 32344191.

11. Stone K. D., Prussin C., Metcalfe D. D. IgE, mast cells, basophils, and eosinophils. J Allergy ClinImmunol. 2010; 125 (2 Suppl 2): 73-80. DOI: 10.1016/j.jaci.2009.11.017. PMID: 20176269; PMCID: PMC2847274.

12. Gigon L., Fettrelet T., Yousefi S., et al. Eosinophils from A to Z. Allergy. 2023; 78 (7): 1810-1846. DOI: 10.1111/all.15751.

13. Valent P., Klion A. D., Roufosse F., et al. Proposed refined diagnostic criteria and classification of eosinophil disorders and related syndromes. Allergy. 2023; 78 (1): 47-59. DOI: 10.1111/all.15544.

14. Akdis C. A. Does the epithelial barrier hypothesis explain the increase in allergy, autoimmunity and other chronic conditions? Nat Rev Immunol. 2021; 21 (11): 739-751. DOI: 10.1038/s41577-021-00538-7.

15. Schleimer R. P., Berdnikovs S. Etiology of epithelial barrier dysfunction in patients with type 2 inflammatory diseases. J Allergy Clin Immunol. 2017; 139 (6): 1752-1761. DOI: 10.1016/j.jaci.2017.04.010.

16. Parrish A., Boudaud M., Kuehn A., et al. Intestinal mucus barrier: a missing piece of the puzzle in food allergy. Trends Mol Med. 2022; 28 (1): 36-50. DOI: 10.1016/j.molmed.2021.10.004.

17. Holden C., Soares P., Fidler K., et al. Children with asthma and eczema carrying filaggrin loss-of-function mutations have increased antibiotic use through to adulthood. ClinExp Allergy. 2024; 54 (4): 291-293. DOI: 10.1111/cea.14440. Epub 2023 Dec 15. PMID: 38100258.

18. Li M. W. Y., Burnett L., Dai P., et al. Filaggrin-Associated Atopic Skin, Eye, Airways, and Gut Disease, Modifying the Presentation of X-Linked Reticular Pigmentary Disorder (XLPDR). J ClinImmunol. 2024; 44 (1): 38. DOI: 10.1007/s10875-023-01637-x. PMID: 38165470.

19. Jerschow E., Dubin R., Chen C. C., et al. Aspirin-exacerbated respiratory disease is associated with variants in filaggrin, epithelial integrity, and cellular interactions. J Allergy ClinImmunol Glob. 2024; 3 (2): 100205. DOI: 10.1016/j.jacig.2024.100205. PMID: 38317805; PMCID: PMC10838899.

20. Gavrilita E., Silion S. I., Bitca M. L., et al. Insights into Intrinsic Atopic Dermatitis: immunogenicity, Dysbiosis, and Imaging (Reflectance Confocal Microscopy, Optical Coherence Tomography). Clin CosmetInvestig Dermatol. 2024; 17: 1377-1386. DOI: 10.2147/CCID.S459096. PMID: 38881699; PMCID: PMC11179656.

21. Freeman S. C., Sonthalia S. Histology, Keratohyalin Granules. 2023 May 1. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025. PMID: 30725734.

22. Saito K., Orimo K., Kubo T., et al. Laundry detergents and surfactants induced eosinophilic airway inflammation by increasing IL-33 expression and activating ILC2s. Allergy. 2023; 8: 1878-1892. https://doi.org/10.1111/all.15762.

23. Celebi Sozener Z., Ozdel Ozturk B., Cerci P., et al. Epithelial barrier hypothesis: effect of the external exposome on the microbiome and epithelial barriers in allergic disease. Allergy. 2022; 77 (5): 1418-1449.

24. Moloudizargari M., Moradkhani F., Asghari N., et al. NLRP inflammasome as a key role player in the pathogenesis of environmental toxicants. Life Sci. 2019; 15 (231): 116585. DOI: 10.1016/j.lfs.2019.116585.

25. Nenasheva N. M. Bronchial asthma. Modern view of the problem. M.: GEOTAR-Media, 2018.304 p. (In Russ.)

26. Albanova V. I., Pampura A. I. Atopic dermatitis. 2nd ed. M.: GEOTAR-Media, 2020. 144 p. (In Russ.)

27. Forno E., Han Y. Y., Mullen J., et al. Overweight, obesity, and lung function in children and adults-a meta-analysis. J Allergy ClinImmunol Pract. 2018; 6 (2): 570-581.

28. Sunadome H., Matsumoto H., Izuhara Y., et al. Correlation between eosinophil count, its genetic background and body mass index: the Nagahama study. Allergol Int. 2020; 69 (1): 46-52. DOI: 10.1016/j.alit.2019.05.012.

29. Zheng H., Wu D., Wu X., et al. Leptin promotes allergic airway inflammation through targeting the unfolded protein response pathway. Sci Rep. 2018; 8 (1): 8905. DOI: 10.1038/s41598-018-27278-4.

30. Michalovich D., Rodriguez-Perez N., Smolinska S., et al. Obesity and disease severity magnify disturbed microbiome-immune interactions in asthma patients. Nat Commun. 2019; 10 (1): 5711. DOI: 10.1038/s41467-019-13751-9.

31. Li Z., Ju Z., Frieri M. The T-cell immunoglobulin and mucin domain (TIM) gene family in asthma, allergy, and autoimmunity. Allergy Asthma Proc. 2013; 34 (1): e21-26. DOI: 10.2500/aap.2013.34.3646. PMID: 23406933.

32. Zhang Y. D., Chen Y. R., Zhang W., et al. Assessing prospective molecular biomarkers and functional pathways in severe asthma based on a machine learning method and bioinformatics analyses. J Asthma. 2025; 62 (3): 465-480. DOI: 10.1080/02770903.2024.2409991. Epub 2024 Oct 12. PMID: 39392250.

33. Martín-González E., Hernández-Pérez J. M., Pérez J. A. P., et al. Alpha-1 antitrypsin deficiency and Pi*S and Pi*Z SERPINA1 variants are associated with asthma exacerbations. Pulmonology. 2025; 31 (1): 2416870. DOI: 10.1016/j.pulmoe.2023.05.002. Epub 2024 Oct 25. PMID: 37236906.

34. Schuler C. F. 4th, Tsoi L. C., Billi A. C., et al. Genetic and Immunological Pathogenesis of Atopic Dermatitis. J Invest Dermatol. 2024; 144 (5): 954-968. DOI: 10.1016/j.jid.2023.10.019. Epub 2023 Dec 11. PMID: 38085213; PMCID: PMC11040454.

35. Avdeev S. N. Patient management tactics in pulmonology: a practical guide. Ed. S. N. Avdeev. M.: GEOTAR-Media, 2025. 280 p. (In Russ.)

36. Adcock I. M., Mumby S. Glucocorticoids. Handb Exp Pharmacol. 2017; 237: 171-196. DOI: 10.1007/164_2016_98. PMID: 27864677.

37. Offermanns S., Rosenthal W. (ed.). Encyclopedia of molecular pharmacology. Cham: Springer International Publishing, 2021. 1593 p.

38. Wadhwa R., Dua K., Adcock I. M., et al. Cellular mechanisms underlying steroid-resistant asthma. EurRespir Rev. 2019; 28 (153): 190096. PMID: 31636089. https://doi.org/10.1183/16000617.0096-2019.

39. Panettieri R. A., Schaafsma D., Amrani Y., et al. Non-genomic effects of glucocorticoids: an updated view. Trends PharmacolSci. 2019; 40 (1): 38-49. PMID: 30497693 PMCID: PMC7106476. https://doi.org/10.1016/j.tips.2018.11.002.

40. Avdeev S. N., Arhipov V. V. Inhalation therapy. Ed. S. N. Avdeev, V. V. Arhipov. M.: GEOTAR-Media, 2022. 400 p. (In Russ.)

41. Rogliani P., Ritondo B. L., Puxeddu E., et al. Experimental glucocorticoid receptor agonists for the treatment of asthma: a systematic review. J ExpPharmacol. 2020; 12: 233-254. PMID: 32982485. PMCID: PMC7495344. https://doi.org/10.2147/JEP.S237480.

42. Emelyanov A. V. Efficacy and safety of inhaled glucocorticosteroids in patients with bronchial asthma (lecture). RMJ. 2018; 3 (1): 20-25. (In Russ.)

43. Golyuchenko O. A., Osochuk S. S. Glucocorticoids immunotropic effects realization: the role of glucocorticoid receptors, transport and regulatory systems. The literature review. Prescription. 2022; 25 (3). 299 p. (In Russ.)

44. Zastrozhina A. K., Zaharova I. N., Sychev D. A. Bronchial asthma: pharmacogenetic approaches to optimization of inhaled glucocorticosteroid therapy. Russian Journal of Allergy. 2019; 16 (3): 26-34. (In Russ.)

45. Matsumura Y. Inadequate therapeutic responses to glucocorticoid treatment in bronchial asthma. J Int Med Res. 2023; 51 (6): 3000605231175746. DOI: 10.1177/03000605231175746. PMID: 37296513; PMCID: PMC10280542.

46. Busby J., Khooa E., Pfefferb P. E., et al. The effects of oral corticosteroids on lung function, type-2 biomarkers and patient-reported outcomes in stable asthma: A systematic review and meta-analysis. Resp Med. 2020; 173106156.

47. Goldsmith L. A., Katz S. I., Gilchrest B. A., et al. Fitzpatrick’s Dermatology General Medicine. Moscow: Izdatel'stvo Panfilova, 2015: 1168 p. (In Russ.)

48. Gether L., Linares H. P. I., Kezic S., et al. Skin and systemic inflammation in adults with atopic dermatitis before and after whole-body topical betamethasone 17-valerate 0.1% or tacrolimus 0.1% treatment: A randomized controlled study. J Eur Acad Dermatol Venereol. 2025; 39 (2): 308-321. DOI: 10.1111/jdv.20258.

49. Wollenberg A., Christen-Zäch S., Taieb A., et al. ETFAD/EADV Eczema taskforce 2020 position paper on diagnosis and treatment of atopic dermatitis in adults and children. J EurAcadDermatolVenereol. 2020; 34 (12): 2717-2744. DOI: 10.1111/jdv.16892. Epub 2020 Nov 17. PMID: 33205485.

50. Sousa-Pinto B., Vieira R. J., Brozek J., et al. Intranasal antihistamines and corticosteroids in allergic rhinitis: A systematic review and meta-analysis. Journal of Allergy and Clinical Immunology. 2024; 154 (2), 340-354.

51. Torres M. I., Gil-Mata S., Bognanny A., et al. Intranasal Versus Oral Treatments for Allergic Rhinitis: A Systematic Review With Meta-Analysis. The Journal of Allergy and Clinical Immunology: In Practice. 2024; 12 (12), 3404-3418.

52. Clinical guidelines "Allergic rhinitis". Non Nocere. New Therapeutic Journal. 2023; (4): 44 52. (In Russ.)

53. Rosenfield L., Keith P. K., Quirt J., et al. Allergic rhinitis. Allergy Asthma. ClinImmunol. 2024; 20 (Suppl 3): 74. DOI: 10.1186/s13223-024-00923-6. PMID: 39731198; PMCID: PMC11681636.

54. Brunton Laurence L., Björn C. Knollmann. Goodman & Gilman's: The Pharmacological Basis of Therapeutics, 14th Edition. Mc Graw Hill. 2023; 1645 p.

55. Farzam K., Sabir S., O'Rourke M. C. Antihistamines. [Updated 2023 Jul 10]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK538188/.