Main Article Content
Intradermal, immunotherapy, house dust mites, Blomia tropicalis, allergy immunotherapy, cost-effective, allergic rhinitis, low dose.
Introduction: Aqueous allergen injections, an effective and century-old technique, is considered a second-line approach in daily clinical practice. Inconveniences still surround conventional subcutaneous immunotherapy (SCIT) administration, such as a need for frequent injections, prolonged up-dosing schedules, elevated costs, and the unlikely possibility of a systemic reaction. The intradermal immunotherapy route (IDR) might favorably impact many of the aforementioned issues (Table 1). House dust mite (HDM) allergens are the main perennial sensitizers in the tropics, and as such, are solely employed in immunotherapy treatments.
Methods: We carried out a year-long real-life study in 25 perennial allergic rhinitis children, symptomatic on exposure to house dust, employing an intradermal low-dose allergen mix consisting of 50 ng of Dermatophagoides pteronyssinus/Dermatophagoides farinae and 120 ng of Blomia tropicalis, under a unique cost-wise protocol. Basal symptoms/signs and face Visual Analog Scale (fVAS) scores were recorded for 2 weeks and later compared with those registered throughout the 1-year treatment. Serum-specific IgG4 and IL-10 levels were employed in the assessment of the immune responses.
Results: Symptoms/signs and fVAS scores were significantly reduced from days 42 and 49, respectively, and remained so until treatment completion. Increases in specific IgG4’s and IL-10 levels reflected significant immune responses. Injections were well tolerated and families reported improved health status (quality of life, QoL).
Conclusions: A unique cost-effective immunotherapy alternative for deprived allergic communities in tropical settings is depicted; further research is needed.
2. Cox L, Nelson H, Lockey R, Calabria C, Chacko T, Finegold I, et al. Allergen immunotherapy: a practice parameter third update. J Allergy Clin Immunol. 2012;127:S1–S55. https://doi. org/10.1016/j.jaci.2010.09.034.
3. Nelson HS. Immunotherapy for house-dust mite allergy. Allergy Asthma Proc. 2018;39:264–272. https://doi.org/10.2500/ aap.2018.39.4145.
4. Eifan AO, Calderon MA, Durham SR. Allergen immunotherapy for house dust mite: clinical efficacy and immunological mechanisms in allergic rhinitis and asthma. Expert Opin Biol Ther. 2013;13:1543–1556. https://doi.org/10.1517/14712598.20 13.844226.
5. Jacobsen L, Wahn U, Bilo MB. Allergen-specific immunotherapy provides immediate, long-term and preventive clinical effects in children and adults: the effects of immunotherapy can be categorized by level of benefit – the centenary of allergen-specific subcutaneous immunotherapy. Clin Transl Allergy. 2012;2:8. https://doi.org/10.1186/2045-7022-2-8.
6. Des Roches A, Paradis L, Knani J, Hejjaoui A, Dhivert H, Chanez P, et al. Immunotherapy with a standardized Dermatophagoides pteronyssinus extract. V. Duration of the efficacy of immunotherapy after its cessation. Allergy. 1996;51:430–433. https:// doi.org/10.1111/j.1398-9995.1996.tb04643.x.
7. Huang Y, Wang C, Wang X, Zhang L, Lou H. Efficacy and safety of subcutaneous immunotherapy with house dust mite for allergic rhinitis: a meta-analysis of randomized controlled tri-als. Allergy. 2019;74:189–192. https://doi.org/10.1111/all.13583.
8. Calderón MA, Frankland AW, Demoly P. Allergen immunotherapy and allergic rhinitis: false beliefs. BMC Med. 2013;11:255. https://doi.org/10.1186/1741-7015-11-255.
9. Rice JL, Diette GB, Suarez-Cuervo C, Brigham EP, Lin SY, Ramanathan M, et al. Allergen-specific immunotherapy in the treatment of pediatric asthma: a systematic review. Pediatrics. 2018;141:e20173833. https://doi.org/10.1542/ peds.2017-3833.
10. Varney VA, Gaga M, Frew AJ, Aber VR, Kay AB, Durham SR. Usefulness of immunotherapy in patients with severe summer hay fever uncontrolled by anti-allergic drugs. BMJ. 1991;302:265–269. https://doi.org/10.1136/bmj.302.6771.265.
11. Varney VA, Tabbah K, Mavroleon G, Frew AJ. Usefulness of specific immunotherapy in patients with severe perennial allergic rhinitis induced by house dust mite: a double-blind, randomized, placebo-controlled trial. Clin Exp Allergy. 2003;33:1076– 1082. https://doi.org/10.1046/j.1365-2222.2003.01735.x.
12. Fujita H, Soyka MB, Akdis M, Akdis CA. Mechanisms of allergen-specific immunotherapy. Clin Transl Allergy. 2012;2:2. https://doi.org/10.1186/2045-7022-2-2.
13. Nelson HS. Injection immunotherapy for inhalant allergens. In: Adkinson NF, Bochner BS, Burks AW, Busse WW, Holgate ST, Lemanske RF, et al., editors. Middleton’s allergy: principles and practice. Philadelphia: Elsevier Saunders; 2014, p. 1416–1437.
14. Cox LS, Hankin C, Lockey R. Allergy immunotherapy adher-ence and delivery route: location does not matter. J Allergy Clin Immunol Pract. 2014;2:156–160. https://doi.org/10.1016/j. jaip.2014.01.010.
15. Jutel M, Rudert M, Kreimendahl F, Kuna P. Efficacy and tol-erability of a house dust mite allergoid in allergic bronchial asthma: a randomized dose-ranging trial. Immunotherapy. 2018;10:1149–1161. https://doi.org/10.2217/imt-2018-0087.
16. Baena-Cagnani CE, Larenas Linnemann D, Gómez M, Díaz SG, Solé D, Borges MS, et al. Allergy training and immunotherapy in Latin America: results of a regional overview. Ann Allergy Asthma Immunol. 2013;111:415–419. https://doi. org/10.1016/j.anai.2013.08.011.
17. Sánchez-Borges M, Fernández-Caldas E, Capriles-Hulett A, Caballero-Fonseca F. Mite hypersensitivity in patients with rhinitis and rhinosinusitis living in a tropical environment. Allergol Immunopathol (Madr). 2014;42:120– 126. https://doi.org/10.1016/j.aller.2012.07.011.
18. Capriles-Hulett A, Iraola V, Pinto H, Sánchez-Borges M, Daboín-De-Veer M, Fernández-Caldas E. Monosensitization to Blomia tropicalis: Is exposure the only factor involved? J Investig Allergol Clin Immunol. 2009;19:165–166.
19. Caplin J, Capriles-Hulett A, Iraola V, Pinto H, Sánchez-Borges M, de los Santos G, et al. Allergic sensitization to domestic mites in Corpus Christi, Texas. Allergy Asthma Proc. 2009;30:166–170. https://doi.org/10.2500/aap.2009.30.3209.
20. Sánchez-Borges M, Capriles-Hulett A, Caballero-Fonseca F, Fernández-Caldas E. Mite and cockroach sensitization in allergic patients from Caracas, Venezuela. Ann Allergy Asthma Immunol. 2003;90:664–668. https://doi.org/10.1016/ S1081-1206(10)61873-X.
21. Caraballo L, Zakzuk J, Lee BW, Acevedo N, Soh JY, Sánchez-Borges M, et al. Particularities of allergy in the Tropics. World Allergy Organ J. 2016;9:20. https://doi.org/10.1186/ s40413-016-0110-7.
22. Sánchez-Borges M, Capriles-Hulett A, Caballero-Fonseca F. Asthma care in resource-poor settings. World Allergy Organ J. 2011;4:68–72. https://doi.org/10.1097/ WOX.0b013e318213598d.
23. Franklin W, Lowell FC. Comparisons of two dosages of ragweed extract in the treatment of pollenosis. JAMA. 1967;201:915– 917. https://doi.org/10.1001/jama.1967.03130120023006.
24. Van-Metre TE, Adkinson NF, Lichtenstein LM, Mardiney MR, Norman PS, Rosenberg GL, et al. A controlled study of the effectiveness of the Rinkel method of immunotherapy for ragweed pollen hay fever. J Allergy Clin Immunol. 1980;65:288– 297. https://doi.org/10.1016/0091-6749(80)90158-X.
25. Ordman D. Allergic desensitization by the intradermal route. S Afr Med J. 1961;29:617–620.
26. Phillips EW. Relief of hay-fever by intradermal injection of pollen extract. JAMA. 1926;86:182–184. https://doi.org/10.1001/ jama.1926.02670290022008.
27. Phillips EW. Intradermal pollen therapy during the attack. J Allergy Clin Immunol. 1933;5:29–36. https://doi.org/10.1016/ S0021-8707(33)90167-7.
28. Rotiroti G, Shamji M, Durham SR, Till SJ. Repeated low-dose intradermal allergen injection suppresses allergen-induced cutaneous late responses. J Allergy Clin Immunol. 2012;130:918– 924. https://doi.org/10.1016/j.jaci.2012.06.052.
29. Benaim-Pinto C, Fassrainer A. Intradermal immunotherapy in children with severe skin inflammatory reactions to Aedes aegypti and Culex quinquefasciatus mosquito bites. Int J Dermatol. 1990;29:600–601. https://doi.org/10.1111/j.1365-4362.1990. tb03479.x.
30. Benson RL. Diagnosis and treatment of sensitization to mosquitoes. J Allergy Clin Immunol. 1936;8:47–59. https://doi. org/10.1016/S0021-8707(36)90119-3.
31. Slovick A, Douiri A, Muir R, Guerra A, Tsioulos K, Hay E, et al. Intradermal grass pollen immunotherapy increases TH2 and IgE responses and worsens respiratory allergic symptoms. J Allergy Clin Immunol. 2017;139:1830–1839. https://doi. org/10.1016/j.jaci.2016.09.024.
32. Vieira-Hernández A, Capriles-Hulett A, Sánchez-Borges M, Fabiano F, Albarrán-Barrios C. [Intradermal immunotherapy with low-dose house dust mite allergens in patients with allergic rhinitis: a proof-of-concept study]. Rev Alerg Mex. 2018;65:41–51. https://doi.org/10.29262/ram.v65i1.322.
33. Cardona R, Sánchez A, Larenas-Linnemann D, Járes E, Sánchez J. [Allergen extracts for immunotherapy in Latin America]. Rev Alerg Mex. 2018;65:25–40. https://doi.org/10.29262/ram. v65i1.287.
34. Mao J, Heithoff KA, Koep E, Murphy T, Hammerby E. Cost of subcutaneous immunotherapy in a large insured population in the United States. Curr Med Res Opin. 2019;35:351– 358. https://doi.org/10.1080/03007995.2018.1510386.
35. Makatsori M, Pfaar O, Calderon MA. Allergen immunotherapy: clinical outcomes assessment. J Allergy Clin Immunol Pract. 2014;2:123–129. https://doi.org/10.1016/j.jaip.2014.01.005.
36. Bousquet PJ, Combescure C, Neukirch F, Klossek JM, Méchin H, Daures JP, et al. Visual analog scales can assess the severity of rhinitis graded according to ARIA guidelines. Allergy. 2007;62:367–372. https://doi. org/10.1111/j.1398-9995.2006.01276.x.
37. Demoly P, Bousquet PJ, Mesbah K, Bousquet J, Devillier P. Visual analogue scale in patients treated for allergic rhinitis: an observational prospective study in primary care: asthma and rhinitis. Clin Exp Allergy. 2013;43:881–888. https://doi. org/10.1111/cea.12121.
38. Casey N. Dying infants and no medicine: inside Venezuela’s failing hospitals. The New York Times [Internet]. 2016 May 15 [cited 1 November 2019]. Available from: https:// www.nytimes.com/2016/05/16/world/americas/dying-in-fants-and-no-medicine-inside-venezuelas-failing-hospitals. HTML
39. Breinbauer H, Varela C, Núñez M, Ugarte S. Encuesta de Síntomas SNOT-20 para rinitis alérgica y rinosinusitis: validación en Chile. Revista Médica de Chile. 2011;139(7):886–895.
40. Oppenheimer J, Tankersley M, Burnett T, Engler D, Filley W, Larenas-Linnemann D, et al. ACAAI’s allergen immunotherapy extract preparation: physician instruction guide [Internet]. American College of Allergy, Asthma and Immunology; 2017 [cited 1 November 2019]. Available from: https://college. acaai.org/allergen-immunotherapy-extract-pr
41. G. Plunkett. Stability of major allergen proteins in extract mixes diluted in human serum albumin (HSA), normal saline (NSP), or glycerin (GLY). J Allergy Clin Immunol. 2007;119:S105. https:// doi.org/10.1016/j.jaci.2006.11.629.
42. Plunkett G, Schell M, Round Rock TX. Stability of allergen extracts diluted in saline or human serum albumin solu-tions [abstract]. Ann Allergy Asthma Immunol. 2010;105:A32. https://doi.org/10.1016/j.anai.2010.09.019.
43. Castro-Almarales, et al. Subcutaneous allergy immunother-apy for asthma: a randomized, double blind, placebo controlled study with a standardized Blomia tropicalis vaccine. World Allergy Organ J. 2020;13:10098. http://doc.org/101016/ jwaojou.2020.10098.
44. Dreborg S. The skin prick test: methodological studies and clinical applications [dissertation]. Sweden: Linköping University; 1987.
45. Allied Market Research. Allergy treatment market to gar-ner $40.36 billion by 2026 [Internet]; 2020 [cited 11 march 2020]. Available from: https://www.globenewswire.com/new srelease/2020/02/13/1984673/0/en/Allergy-Treatment-Market-to-Garner-40-36-Billion-by-2026.html
46. Market Watch. Allergy Immunotherapy Market Share, Size 2020 Analysis, Growth By Top Companies, Trends By Types and Application, Forecast Analysis To 2024 Says Market Reports World [Internet]; 2020 [cited 11 march 2020]. Available from: https://www.marketwatch.com/press-release/allergy-immunotherapy-market-share-size-2020-analysis-growth-by-top-companies-trends-by-types-and-application-forecast-analysis-to-2024-says-market-reports-world-2020-03-11
47. Francis NJ, James LK, Paraskevopoulos G, Wang C, Calderon M, Durham SR, Till SJ. Grass pollen immunotherapy: IL 10 induc-tion and suppression of late responses precede IgG4 inhibitory antibody activity. J Allerg Clin Immunol. 2008:121(5):1120– 1125. https://doi.org/10.1016/j.jaci.2008.01.072
48. Romani N, Ebner S, Tripp CH, Flacher V, Koch F, Stoitzner P. Epidermal Langerhans cells – changing views on their function in vivo. Immunol Lett. 2006 Aug 15;106:119–125. https://doi. org/10.1016/j.imlet.2006.05.010.
49. Asokananthan N, et al. House dust mite allergens induced proinflammatory cytokines from respiratory epithelial cells: the cysteine protease allergens, Der p1, activates protease activated receptor (PAR)-2 and inactivates PAR – 1. J Immunol. 2002;169:4572–4578. https://doi.org/10.4049/ jimmunol.169.8.4572
50. Slovick A, Douiri A, Muir R, Guerra A, Tsioulos K, Haye E, et al. A randomised placebo-controlled trial investigating efficacy and mechanisms of low-dose intradermal allergen immunotherapy in treatment of seasonal allergic rhinitis. EME.2016; 3: 1-79. https://doi.org/10.3310/eme03100.
51. Capriles-Hulett A, Sánchez-Borges M. Providing feasible solutions for an asthmatic impoverished population. Chapter 10. In: Mahdavinia M, editor. Health disparities in allergic diseases. An evidence-based look at causes, conditions, and outcomes. Switzerland: Springer Nature Switzerland AG, Cham; 2019. p. 207–216. https://doi.org/10.1007/978-3-030-31222-0_10