We all want a better life, and hay fever patients are no exception: allergen immunotherapy can help them achieve that.
Imagine nature’s rebirth in spring. The longer, sunnier days, bright colours, thousands of flowers, the fragrant air and the irresistible energy of life all around you. Well, if you are a hay fever sufferer, you might cringe and instinctively check your medicines cabinet.
Seasonal allergic rhinitis, or hay fever, is an allergic inflammation of the upper airways, triggered by pollen suspended in the air.
An outsider might think this is not a serious health condition… so what if you sneeze or your eyes itch? However, the patients will likely disagree. Research has shown that their quality of life can be significantly affected during the pollen season (1). Furthermore, rhinitis is a recognised risk factor for asthma (2), and some patients are at risk of life-threatening allergic reactions (3). Food allergies can also accompany pollen sensitisation (4). This is logical, if we think that pollen granules are parts of plants.
About a quarter of the UK population suffer from rhinitis. Its prevalence has continually increased over the past 50 years (2) (a valid question and perhaps an interesting discussion for another time is why this happened).
Which are the offending pollens?
Firstly, are all flowers potential culprits?
Allergenic pollen comes from trees, grasses and weeds. However, some of these sources may not even look like what you normally identify as flowers. Or, they are so inconspicuous that you may not give them a second thought. Some pollinate at the end of winter, thus the thought of blaming pollen for symptoms may even seem a bit far-fetched.
Allergenic flowers produce tiny pollen grains that can easily become airborne and consequently end up in patients’ airways. In some people, these minute structures trigger an allergic response in the airways. This means they stimulate the immune system to produce a certain kind of antibody (called IgE or immunoglobulin E).
In the UK, the main sources of allergenic pollen are alder, ash, birch, oak, pine, willow, hazel, grass, mugwort, plantain, dock, sorrels, nettle (5), and possibly in the future the fast-invading ragweed (6). Thus, hay fever patients may benefit from immunotherapy with some of these pollens.
Here are a few photos for those unfamiliar with their offenders:
What is allergic inflammation?
Inflammation is the immune system’s response to the danger it perceives. It is what happens when the body sustains a physical injury and the area becomes red, warm, swollen and painful. It is also what happens when bacteria or viruses start to multiply inside the body and the immune system recognises them as invaders. These events are protective and they occur in all people with normally functioning immune systems.
However, in some people, the immune system learns to build an allergic immune response against things that are innocuous to most people. These triggers may be foods, pollen, moulds, medicines etc.
As discussed, immune cells produce IgE antibodies against these substances. These antibodies are bound to the surface of ubiquitous immune cells, acting as ‘sensors’. The IgE-carrier cells are abundant wherever the internal environment comes into contact with the external environment: in our skin, digestive tract, respiratory system, plus around blood vessels. Therefore, they can quickly react to whatever the immune system has identified as dangerous and send signals throughout the body. These sentinels are the mast cells, the master-orchestrators of allergic reactions.
Allergens are substances with the capacity to elicit an allergic immune response. They bind the IgE molecules on the surface of mast cells and activate the latter. This leads to an immediate release of pro-inflammatory substances (e.g., histamine) and triggers the production of further immunologically active compounds by mast cells (e.g., prostaglandins, leukotrienes and cytokines). A cascade of immune activation ensues. Immune cells specific to the allergic inflammation are attracted to the place of allergenic threat. The chemicals released by all these cells, lead to the well-known symptoms of allergy. In the case of hay fever, the symptoms may be itching, runny nose, sneezing, nasal blockage.
What can we do about hay fever?
We can do a lot to control the symptoms of hay fever, starting with measures to avoid exposure to pollen, all the way to medication such as antihistamines, corticosteroids and mast cell stabilisers, or surgery to correct structural issues (7).
However, the ultimate treatment is the one that addresses the disease mechanism. Allergen immunotherapy, or desensitisation, is the only conventional treatment which has the capacity to modify the disease course (cure allergies) and thus offer long-term benefit in hay fever. Its aim is to shift the immune response to allergens, by achieving immune tolerance.
How does immunotherapy work?
Allergen immunotherapy (AIT) is basically a chronic (long-term) exposure to a problematic allergen. The administration can be via injections (subcutaneous immunotherapy – SCIT), or sublingual (SLIT), and starts with incremental doses until reaching a maintenance dose. In the case of SCIT, injections are initially administered weekly during up-dosing, then monthly for at least 3 years. In SLIT, drops or tablets are placed under the tongue, and, unlike SCIT, it can be self-administered at home after initiation under supervision.
There is emerging interest in alternative routes for immunotherapy delivery, such as epicutaneous (via skin application) or intralymphatic (via injections). However, evidence on efficacy and safety is not as strong yet as for SCIT and SLIT (8).
This controlled stimulation of the immune system promotes regulatory T cells, a type of immune cell involved in immunologic tolerance, as well as other cells and chemical mediators which achieve the same goal of quieting down the immune system’s response (8). One marker of successful immunotherapy is the increase in specific antibodies from a different subclass: IgG4. Their significance has been controversial, but recent evidence supports their active role in modulating the allergic reaction (9).
Immunotherapy controls allergy symptoms by reducing their cause: the allergic inflammation.
In pollen allergy, AIT administration can be either on a regular basis for years, or as pre-seasonal treatment. It is not clear though if the latter leads to the same long-term benefit as continuous immunotherapy.
Besides its possible use in hay fever, immunotherapy can have other indications, such as venom or food allergy.
What are the potential benefits and limitations of immunotherapy for hay fever?
The main benefit of AIT, as suggested, is modifying the course of the allergic disease. Ideally, this would mean freedom from symptoms upon exposure to the allergen, improved quality of life (10), and no need for medication. If that sounds like good way to cope with the pollen season, then how about the extra benefit it may have in some cases, of preventing new allergies, preventing progression of allergic rhinitis to asthma, and on asthma severity (8)?
Some may think – if such a treatment is possible, then why bother with a handful of drugs and elaborate avoidance measures?
As with any treatment, AIT has counter-indications and may have adverse effects. Furthermore, the recommendation for immunotherapy takes into consideration patient and disease characteristics. Thus, the number of allergic sensitisations, comorbidities (other diseases the patient has) and the response to symptomatic treatment, all contribute to the decision to recommend immunotherapy. Then, there is the decision on when is the optimal moment to start, the best route of administration, which allergen and which commercial product to use, whether to use continuous or pre-seasonal AIT, and when to stop. Immunotherapy is a long-term treatment that requires commitment and adherence to the recommended administration scheme. It is also expensive.
However, the evidence base is strong for immunotherapy’s benefits in qualifying patients (8) (and we’re talking about moderate or severe hay fever, sub-optimally controlled by medication, or even milder cases wishing to avail of the long-term benefits of AIT in allergic disease prevention).
What if hay fever immunotherapy is counter-indicated?
Unfortunately, there are conditions where AIT is not suitable, including severe asthma and active uncontrolled autoimmune conditions (8).
However, hope is not lost. On the contrary, there are other comprehensive approaches to achieve immune modulation. And, the best thing is that they have the potential to benefit both allergy and autoimmunity.
The paradigm is starting to shift in allergy and autoimmunity with emerging evidence about systems biology approaches, the role of epithelial barrier integrity (11), microbiota (the germs that naturally colonise parts of the human body) (12), toxic exposures (13) and epigenetic changes (alterations in how genes are expressed, caused by environmental factors) (14). Functional Medicine has always promoted such integrated and holistic approaches that aim to restore balance in how the body functions.
There are many more ways to assess allergic patients than measuring IgE. Also, there are many more solutions beyond avoidance of triggers, symptomatic medication, or even the revolutionary allergen immunotherapy.
In conclusion, it is good to have medication available to control your hay fever symptoms. It is even better to consider solutions that act on the root-cause and the mechanism of the allergic reaction.
In our clinic, at The Allergy-Immunology Doctor, we use the best of both worlds, and we leave no stone unturned in our effort to promote immune balance and resilience.
You may want to book a free discovery call to find out how suitable is our approach for your current goals.
1. Papapostolou G, Kiotseridis H, Romberg K, Dahl Å, Bjermer L, Lindgren M, et al. Cognitive dysfunction and quality of life during pollen season in children with seasonal allergic rhinitis. Pediatr Allergy Immunol. 2021;32(1):67–76.
2. 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). Clin Exp Allergy. 2017;47(7):856–89.
3. Lam HCY, Turner PJ, Hemming D, Jarvis DL. Seasonality of food-related anaphylaxis admissions and associations with temperature and pollen levels. J Allergy Clin Immunol Pract [Internet]. 2021;9(1):518-520.e2. Available from: https://doi.org/10.1016/j.jaip.2020.07.032
4. Li J Da, Du ZR, Liu J, Xu YY, Wang RQ, Yin J. Characteristics of pollen-related food allergy based on individual pollen allergy profiles in the Chinese population. World Allergy Organ J [Internet]. 2020;13(5):100120. Available from: https://doi.org/10.1016/j.waojou.2020.100120
5. McInnes RN, Hemming D, Burgess P, Lyndsay D, Osborne NJ, Skjøth CA, et al. Mapping allergenic pollen vegetation in UK to study environmental exposure and human health. Sci Total Environ [Internet]. 2017;599–600(April):483–99. Available from: http://dx.doi.org/10.1016/j.scitotenv.2017.04.136
6. Chapman DS, Scalone R, Štefanić E, Bullock JM. Mechanistic species distribution modeling reveals a niche shift during invasion. Ecology. 2017;98(6):1671–80.
8. Alvaro-Lozano M, Akdis CA, Akdis M, Alviani C, Angier E, Arasi S, et al. EAACI Allergen Immunotherapy User’s Guide. Pediatr Allergy Immunol. 2020;31(S25):1–101.
9. James LK, Till SJ. Potential Mechanisms for IgG4 Inhibition of Immediate Hypersensitivity Reactions. Curr Allergy Asthma Rep. 2016;16(3):1–7.
10. Filanowicz M, Szynkiewicz E, Cegła B, Bartuzi Z. Analysis of the quality of life of patients with asthma and allergic rhinitis after immunotherapy. Postep Dermatologii i Alergol. 2016;33(2):134–41.
11. Hellings PW, Steelant B. Epithelial barriers in allergy and asthma. J Allergy Clin Immunol [Internet]. 2020 Jun;145(6):1499–509. Available from: https://pubmed.ncbi.nlm.nih.gov/32507228
12. Huang YJ, Marsland BJ, Bunyavanich S, O’mahony L, Leung DYM, Muraro A, et al. The microbiome in allergic disease: Current understanding and future opportunities. J Allergy Clin Immunol [Internet]. 2018;139(4):1099–110. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5899886/pdf/nihms955082.pdf
13. Yang SN, Hsieh CC, Kuo HF, Lee MS, Huang MY, Kuo CH, et al. The effects of environmental toxins on allergic inflammation. Allergy, Asthma Immunol Res. 2014;6(6):478–84.