Definition
Allergic rhinitis (AR) consists of findings resulting from an inflammatory hypersensitivity reaction against airborne allergens (aeroallergens) in the nasal tissue.
Epidemiology
AR is the most common chronic disease in Turkey. In 10-30% of the society; AR is found in almost 20-40% of children. Although AR is not a very serious disease, it causes serious socio-economic loss in milk; so to speak, it is a “disease that does not kill but sustains”. It is one of the most important reasons for applications made to family physicians providing primary health care services. Labor limits school performance and socialization. In addition, diseases accompanying AR (such as conjunctivitis, sinusitis, fluid accumulation in the middle ear, nasal polyps, asthma, sleep disorders and urticaria plaques) are also extremely important and often cause the patient to consult a doctor. The way to fully understand AR and its accompanying conditions and the response to the treatment to be applied in these cases is to know the mechanisms of the disease (pathophysiology) well.
Pathophysiology
Allergens
Airborne Allergens
Respiratory allergic diseases are caused by a hypersensitivity reaction to airborne allergens. While pollen and mold fungi create seasonal AR (MAR); House dust mites, household allergens composed of animal proteins create perennial AR (PAR). In order for a pollen to cause symptoms in any area, it must have been in the air for a long time and in large quantities. Almost all of these pollen use the wind for plant fertilization. Pollens that provide fertilization by being carried by insects (flower pollen) cannot be breathed because they are not dependent on air and therefore do not cause an immune response. Tree pollen (March-April), grass pollen (May-June) and weed pollen (mid-August-October) are the most important MAR causes in Turkey. In addition to pollen, molds such as Alternaria, Aspergillus and Cladosporium are also responsible for the findings. The sporulation season of molds is very variable. It is determined by the weather conditions. Most sporulation occurs in any period between March and October. Climate changes in recent years have affected the length and region of these periods.
Although PAR continues throughout the year, non-seasonal rhinitis is also included in this definition. The most important causes are: indoor fungi (their growth is associated with humidity); allergens of animal origin [cat (most prominent) and rodents (mouse, hamster, rat, ferret, rabbits, dogs, birds)]; house dust mites from the genus Dermatophagodies, particularly active from August to December, breeding in carpets, beds, sofas and pillows; insects (best known are cockroaches; however, moths, weasels, crickets, ladybugs, spiders are also effective). House dust mites and cats are the most important source of allergens. House dust mites grow well in places with humidity greater than 55%. Therefore, house dust mite allergy is common in western and southern coastal regions of Turkey and in coastal regions such as Marmara. House dust mites can be found in all areas that remain humid for more than 6 months of the year.
Immunoglobulin E/Mast Cells/Basophil Activation
From a pathophysiological point of view, AR has traditionally been defined as: the cross-linking of an allergen-specific preformed IgE molecule on the surface of mast cells with aeroallergens, resulting in the cross-linking of these mast cells with aeroallergens. It is a disease that occurs with the molecules released into the environment after the explosion (degranulation) of the granules. In all antibody-dependent immune responses except allergic diseases, after the first exposure to foreign molecules (antigen), low-affinity IgM antibodies are produced from B lymphocytes and released into the environment. However, in genetically predisposed individuals (atopic individuals); Repeated exposure to the allergen causes a shift of the immune response to antibodies of the IgE type. As a result, IgE antibodies are released into the circulation. These antibodies of the IgE type go and sit on their specific sites (receptors) on the surface of cells such as mast cells and basophil cells. After repeated allergen exposure, these antibodies cross-link with the allergen (at least two IgE antibodies are bound by the allergen), and the granules inside these cells become empty. A number of chemical molecules (the most important of which is histamine) that spread through the granules to the environment are responsible for allergic effects. It is necessary to repeat this process at least 3-4 times in order to develop an AR that can cause symptoms. That is, for the allergen-specific IgE molecule to concentrate on the mast cell surface enough to cause degranulation, the patient must have been exposed to the allergen during more than one allergy season. Therefore, exposure to the same pollen for at least 3-4 seasons is necessary for the development of symptomatic MAR. For this reason, MAR is not generally seen in infants, so signs of this disease in a person’s life can occur at the earliest around 4 years of age. Similarly, adults must have lived in that area for about 4 years in order to show signs of exposure to local allergens as a result of displacement.
After allergen exposure, mast cells with attached IgE on their surface release a number of newly synthesized and stored chemical molecules (mediators). These mediators include histamine, proteases (tryptase, chymase), leukotrienes, prostaglandins and cytokines. Some of these mediators constitute the early signs of AR. Early phase symptoms include runny nose, itchy nose, sneezing and nasal congestion. Other mediators cause inflammatory cells to come and settle in the nasal mucosa. These inflammatory cells; It consists of cells such as basophil, eosinophil, mast cell. The arrival of inflammatory cells in this area causes a second wave of inflammation. These cells secrete new mediators of their own and are responsible for the late phase reactions of AR. This slowly developing inflammatory response is primarily characterized by intranasal edema (nasal congestion). In addition to the IgE receptors on mast cells and the number of surface-bound IgE, signal transmission increases with chronic allergen stimulation; In this way, mast cells also play a role in enhancing the initiation of the event. This is because as the allergic seasons progress, less allergen is needed for mast cell degranulation.
Antigen Presenting Cell/Helper T Cell Activation
Apart from stimulating mast cells, allergens are perceived as foreign and presented to helper T (Th) cells by antigen presenting cells. As a result of the stimulation of antigen-presenting cells (mononuclear cell, phagocytic cell, dendritic cell and B lymphocyte), some cytokines (cell-to-cell messengers) are released from these cells. Among these cytokines; IL-1, IL-6, TNF-α can be counted and these are important cytokines responsible for innate immunity. With the development of allergic inflammation, an increase in the number of immunoglobulins on the surface of B cells and high-affinity IgE receptors on the surface of dendritic cells occurs. These antibodies actually act as allergen receptors, capturing the antigen and taking part in the processing of the antigen. In allergic patients, helper T lymphocyte activation develops in the direction of Th2, and cytokines such as IL-4, IL-5, IL-9, IL-13, GM-CSF are released from these cells. These cytokines are the leading actors of the inflammatory response in AR. In addition, these cytokines are responsible for the proliferation and activation of eosinophils, mast cells and basophils, and their recruitment to the allergy area. IL-4 and IL-13 are the most important cytokines responsible for IgE production. Therefore, these cytokines are the most important stimuli of allergen-specific IgE formation.
The inflammatory process that develops after exposure to an allergen is a process initiated by mast cells in the environment and continued by eosinophils, basophils, mononuclear cells and helper T cells. The complaints of sneezing, runny nose and itching in AR are mostly caused by the release of molecules such as histamine. As MAR and PAR continue, cytokines and other molecules released from cells in that area cause more mucus release, tissue edema, enlargement of mucus-secreting cells, and tissue damage. These constitute the main source of findings in allergic patients. As AR progresses, the effectiveness of antihistamines decreases as the role of histamine decreases.
Eosinophils are one of the major causes of inflammation in PAR; they also cause progress in the MAR. Eosinophils secrete a wide variety of proinflammatory molecules (such as cysteinyl leukotriene, LT-C4, LT-D4, LT-E4; ECP, eosinophil peroxidase, MBP, IL-3, IL-5, GM-CSF, PAF). . These eosinophil-derived mediators constitute the main components in the chronic allergic response and are also responsible for AR findings such as intranasal edema. The classic story in MAR is the exacerbation of symptoms within weeks with ongoing allergen exposure. Usually the symptoms do not get worse before the pollen count peaks, but it persists for some time after the pollen count has decreased. There is a close relationship between the placement of eosinophils in the nasal mucosa and the development and progression of the findings. In summary, AR; It can be classified as mast cell-mediated, antihistamine-responsive “acute form” and chronic inflammatory process-related, eosinophil-mediated, less responsive to antihistamines “chronic form”.
Clinical Symptoms
The history of the disease is helpful in the diagnosis of AR. The patient has complaints such as sneezing, runny nose (watery discharge), nasal congestion, itching in the nose and palate. These complaints are often accompanied by allergic conjunctivitis (eye fever), in which there are complaints of itching, watering and stinging in the eye. Severe conjunctivitis in PAR is rarer than in MAR. Because the pollen coming from the air also affects the eyes. However, it is difficult for indoor allergens to reach the eyes because the air is more stable. These allergens in the closed environment are taken by breathing more into the nose.
AR is a systemic disease accompanied by circulating activated T lymphocytes and phagocytic, monocytic cells. Activation of these cells and cytokines produced such as IL-1, TNF-α, IL-6 are responsible for findings such as weakness, fatigue, joint and muscle pain in AR. AR also impairs cognitive functions in school children and adults. In fact, these systemic findings are usually the main complaints of allergy sufferers. The patients’ quality of life is highly impaired; They have difficulty doing normal activities such as going to work or school.
diagnosis of AR; It is based on a review of the findings and the history of whether these findings occurred after allergen exposure. Since the disease is genetically transmitted from generation to generation, family history should also be questioned. However, some patients may be the first case in the family.
On examination, the nasal mucosa is pale, sometimes purplish-cyanotic and swollen. There are signs of discharge like water in the nose. In children, even before the examination starts, a horizontal line may be noticed on the nose due to itching by frequently stroking the nose upwards with the hand; Apart from this, high palate, mouth breathing, and tooth position defect can be seen. Due to the enlargement of the veins around the eyes and especially under the eyes, bruises can be noticed.
The definitive diagnosis of AR is made by the demonstration of allergen or allergen-specific IgE antibodies. In addition to the diagnosis, the presence of IgE specific for allergens is decisive for the definitive treatment and prevention methods. skin test; It is a safe, rapid, specific diagnostic test used to detect the relevant allergen. However, it must be done and interpreted by allergy and immunology specialists. Intradermal (injection of allergen into the skin) tests should be performed with the decision of an immunology and allergist; because it can rarely cause a general reaction and be life-threatening. In cases where the patient has a sensitive skin structure such as dermographism or the use of antihistamines, antiemetics (anti-nausea), antipsychotics, and antidepressants, blood allergen or allergen-specific IgE tests should be performed in cases where the test cannot be performed. Requesting these tests by an immunology and allergist will eliminate the unnecessary expense and cost burden. But; these tests are less sensitive than skin tests. Positive results consistent with the findings enable the diagnosis of AR and the regulation of environmental factors; but they cannot be used for the selection of immunotherapy (vaccine) content to be used for radical solution. Finding negative or near-negative values in a patient whose findings are clearly present does not detract from the diagnosis of the disease. They indicate that we need to do more research in such cases.
Differential Diagnosis
It can be difficult to distinguish viral rhinitis from MAR. Viral rhinitis develops independently of mast cell mediators. The main molecule (mediator) obtained in the examination of nasal discharges of patients with colds is “quinine”. Leukotrienes and prostaglandins are other non-dominant mediators. By observing their complaints, many allergic patients can tell the difference between symptoms related to the common cold and allergen exposure. AR differs from viral rhinitis with nasal itching, episodes of sneezing/sneezing, watery runny nose, and a history of recurrence in the same season every year. In viral rhinitis, there is a darker, colored discharge rich in neutrophils (inflammation cells) as the cell in the discharge. Ocular findings are usually not prominent, nasal mucosa is edematous, swollen and reddish on physical examination.
Thyroid hormone deficiency (hypothyroidism), use of birth control drugs, hormonal changes such as pregnancy and menopause may cause edema in the nose. Caused by long-term use of drugs that cause intranasal edema and temporarily relieve congestion (nasal decongestant); chronic reflex vasodilation (vasodilation); Unfortunately, it is the cause of the picture called “medicomentous rhinitis”, which goes with severe nasal congestion. In addition, although it is not common in our country, cocaine use is one of the most common causes of medicamentous rhinitis abroad. Fracture or crookedness in the nasal midline (nasal septum), polyps, tumors, foreign bodies are other causes of chronic nasal congestion. Patients with persistent and unilateral nasal obstruction should be evaluated with a rhinoscopy instrument and computed tomography. Nasal septum deviation can sometimes even cause bilateral nasal congestion; however, the corrective effect of the surgery performed to correct this is very limited.
Abnormal neurogenic response to irritants (cold air, pollution, cigarette smoke, pungent odors, perfume, alcohol, foods) is the main feature of another nasal disease called “vasomotor rhinitis”. In this disease, the autonomic nervous system functions abnormally. Generally, patients may have symptoms such as nasal congestion and post-nasal drip in cases such as air change, hot-cold change. However; There is no itching, sneezing, runny nose, conjunctivitis and systemic complaints in the nose. Allergy tests of these patients are negative and there are no eosinophils in the nasal fluid. Nasal sprays containing azelastine, nasal sprays with cortisone, atropine (nasal sprays containing ipratropium) often provide effective treatment.
Findings in chronic sinusitis with or without nasal polyps; runny nose consists of dark and colored nasal discharge. Computed tomography is usually required to diagnose sinusitis.
In the disease called atrophic rhinitis, atrophy of the nasal epithelium, edema in the nose and a bad smell in the nose are detected on examination. Atrophic rhinitis is more common in older individuals; however, the most common cause of atrophic rhinitis; It is the loss of vessels (devascularization) caused by nasal trauma and surgeries.
Inflammation with eosinophilic cell accumulation but not an allergic condition is defined as “eosinophilic syndrome without AR (NARES)”. These patients also develop chronic sinusitis and nasal polyps in the later stages. The findings of these patients are similar to those of vasomotor rhinitis patients. Diagnosis in NARES is made by examining the nasal swab for eosinophils. Compared to vasomotor rhinitis, NARES responds better to intranasal cromolyn and corticosteroids. Some allergist and immunology specialists now use the definition of “local AR” for this disease. In this case called local AR, although it is not possible to detect an allergen-specific IgE with blood or skin test, a positive response is obtained from allergen spraying (provocation) tests done for research purposes. However, the allergen sensitivity detected here does not have a role in determining radical treatments as in classical AR treatment.
Systemic Indicators of Allergic Rhinitis
Due to inflammation in AR, the nasal openings of the sinuses may be closed, which may cause acute (bacterial) sinusitis. In cystic fibrosis, immotile cilia syndrome, immunodeficiencies, non-specific inflammation, hypersensitivity to colonized fungi (allergic fungal sinusitis), aspirin-exacerbated respiratory diseases (Sampter syndrome), and chronic hyperplastic eosinophilic sinusitis (CHES), chronic sinusitis occurs with chronic bacterial inflammations. . In the absence of cystic fibrosis and immunodeficiency, the source of chronic sinusitis is usually not infection. Half of patients with chronic sinusitis have CHES. The focus is on the underlying allergic mechanisms in these patients. Sensitivity to multiple allergens and perennial allergens (such as house dust mites) poses a risk for the development of CHES. Abnormal radiological findings of the sinuses are detected in more than 50% of patients with PAR. In healthy individuals, allergens are not expected to reach the sinus cavities (allergens do not reach the sinuses by breathing). Since the cavities are clogged in sinusitis, allergens are not expected to reach the sinuses. It has been shown that the particles cannot reach the sinuses in studies with ragweed (American cold herb) labeled with radio-active substance. Therefore, the relationship between AR and sinusitis is provided by the systemic inflammatory response. Moreover; During exacerbations of MAR, intranasal allergen injection (provocation) test performed on sensitive individuals and radiological examinations of these individuals showed that eosinophils were collected in their sinuses and their CHES condition worsened.
In the nasal allergen provocation test performed in patients with MAR accompanied by asthma, it was determined that allergens did not reach the lungs. However, with this test, many lung parameters were deteriorated in terms of allergy and immunological indicators (such as increased presentation of adhesion molecules and eosinophil accumulation and increased bronchial hyperactivity). As a result of allergen exposure, immune cells such as helper T lymphocytes, dendritic, mononuclear, mast cells and eosinophil precursor cells are activated in the nose and nasal lymphatic tissues. Some of the activated helper T cells migrate to the bone marrow and stimulate the production of basophils, eosinophils, mast cell precursors that will play a role in allergic inflammation in the bone marrow. As a result, newly formed inflammatory cells enter the circulation and are selected into the sinuses in patients with CHES; It also reaches the lungs in asthmatic patients.
When we look at all these findings, AR is not just a disease limited to the nasal mucosa. Associated with systemic inflammation; therefore, AR is often accompanied by diseases such as asthma, secretory otitis media and CHES.
Prevention and Environmental Control
If contact with the allergen source can be avoided, a treatment option exists for AR patients. In AR, unlike asthma, there is insufficient data on allergen protection. In addition, the amount of allergen that needs to be protected in order to regress the symptoms is not known. Studies in asthma show that prevention therapy reduces bronchial hyperresponsiveness, severity of symptoms, and the need for rescue (β-agonist) drugs.
There are 4 basic ways to protect against house dust mites:
1) Removal of substances that create an environment for mite reproduction (covering bedding and pillows with allergen-proof covers, removing carpets and fabric-covered furniture from the bedroom).
2) Keeping the humidity below 50%.
3) Washing bedding with hot water (55°C or hotter). Because cold water washing and drying do not kill mites.
4) Wearing a mask when dust is removed at home and until 10 minutes later; It provides protection from large allergen molecules.
Reducing humidity also acts against fungi. Windows and shower curtains are suitable places for the growth of fungi. These fungi are easily cleaned with fungicides (diluted bleach).
There are many cockroaches in some houses, especially in apartments in big cities, and sensitivity to cockroach allergens is common. Although it is difficult to clean the apartment from cockroaches by killing insects, the use of chemical sprays and traps helps. Since chemical spray can disturb asthma patients, care should be taken in their use.
Closing windows and using ventilation reduces seasonal allergen exposure. In addition, since the air is dried with ventilation, the suitable environment for the reproduction of mites and fungi is deteriorated.
Pets such as cats; It is the source of the most important allergens that can be removed in AR. The skin rash of pets accumulates and its effects continue for a long time (about 6 months) after the pet (cat, dog, rodent) is removed. Keeping dogs outside of the house, washing them frequently, and taking them home occasionally usually solves the problem. However, cat allergy is more serious because cats store large amounts of allergens. Cat owners can also store allergens when they are with the cat, causing symptoms at school and in their allergic counterparts. The most important source of rodent allergens is rodent urine, and like cats, rodents cause large amounts of allergen storage in the home.
Treatment
Although prevention methods in allergic diseases reduce allergen exposure and reduce symptoms, this method alone is not enough; medication or other treatment methods are often required.
Evidence-Based Therapy
Antihistamines
Antihistamines are one of the oldest drugs used in the treatment of allergic diseases and constitute the first step in the treatment of AR. Antihistamines bind to H1 receptors (alcophagus) to which the leading actor, which causes sneezing, itching, runny nose and conjunctivitis, causes allergic disease symptoms called histamine, to which it will adhere to show its effects. These drugs generally improve AR-related findings, albeit temporarily. But; antihistamines do not have sufficient effect on the finding of nasal congestion. Other than blocking histamine receptors, some antihistamines also reduce mast cell lysis (degranulation). Such antihistamines are called dual-acting antihistamines. After the use of these drugs, a decrease is observed in both free circulating histamine in the blood and other mast cell-derived mediators (cysteinyl leukotrienes). First generation antihistamines, which are the oldest forms of antihistamine drugs, can easily reach the brain by crossing the blood-brain barrier and therefore cause drowsiness, distraction, forgetfulness, etc. can produce findings. It can reduce school success because it causes sleepiness; they interfere with activities such as work, driving, and using machinery. Clinically, only 10-15% of all patients complain of these side effects. However, on a research basis, decreased motor activity, decreased driving ability, and slowed electroencephalographic (EEG) response are detected with first generation antihistamines (chlorpheniramine, diphenhydramine, clemastine) in all patients. Therefore, long-term use of these drugs is not appropriate. It is stated that second generation antihistamines, which are free of most of these side effects, have a longer duration of action and do not show the undesirable effects that occur with first generation antihistamines, since they generally do not cross the blood-brain barrier. However, clinically, side effects such as drowsiness, distraction, and concentration disorder are not uncommon. Second-generation antihistamines include loratadine, descarboxyloratadine, fexofenadine, and cetirizine. This group of drugs literally does not have much superiority over each other in terms of effect or side effects.
Intranasal antihistamine; Although the use of azelastine does not produce a faster response than oral antihistamines, it also improves sleep, etc. It has less side effects such as non-allergic rhinitis and interestingly creates an anti-edema effect.
As I mentioned earlier in my article, the role of histamine decreases as the allergy season progresses. In addition, the role of histamine in PAR has decreased. This situation causes us to get enough effectiveness from antihistamines. In addition, drug insensitivity (tachyphylaxis) develops rapidly to long-term antihistamine drugs. Therefore, atihistamines are highly effective in acute allergic reactions caused by mast cell-derived histamine and should be used in these situations.
Decongestants (edema suppressants)
Decongestants such as pseudoephedrine are mild-acting drugs that relieve nasal congestion. These drugs are often used in conjunction with antihistamines to relieve all complaints of AR patients. However; The use of antihistamines and decongestants usually does not improve patients with moderate to severe AR.
Leukotriene Blocking Drugs
Drugs that block molecules called leukotrienes (zileuton, zafirlukast, montelukast) have proven effectiveness in some cases compared to antihistamines. This activity reflects the importance of proinflammatory and vasoactive mediators in the pathophysiology of AR. In some studies and observations, it is stated that zafirlukast controls sneezing, nasal discharge and especially nasal congestion better than antihistamines in patients with MAR. Similarly, montelukast; It provides improvement in nasal and eye symptoms and quality of life in patients with MAR and PAR.
Nasal (Intranasal) Cromolyn
Cromolyn basically stabilizes mast cells and prevents them from degranulating. In addition, it has an anti-inflammatory effect on macrophages and T lymphocytes. Although cromolyn is not as effective as intranasal corticosteroids, it provides improvement in patients with mild to moderate symptoms. They can be used in combination with corticosteroids in patients with persistent symptoms. The most important problem is that the medicine must be sprayed into the nose 3-4 times a day. It does not show effectiveness in 30-40% of patients. Cromolyn (1-2 times in each nostril every 3-4 hours) is used specifically as a prophylactic (for example, just before cat exposure or 1-2 weeks before allergic season).
Cromolyn applied as eye drops is used in the treatment of allergic conjunctivitis.
No side effects were observed with the use of cromolyn.
Nasal (Intranasal) Corticosteroid
Corticosteroids have been shown to be effective drugs in local use. It has been shown that the use of local antihistamines in addition to the drug has no significant additional effect. It has been shown that 50-90% reduction in symptoms is achieved with the use of local corticosteroids (this rate is around 20-30% for local antihistamines). Aksırma, kaşıntı, burun akıntısı, burun içi ödem ve konjunktivite de (bazı çalışmalarda) etkilidir. Birkaç çalışmada AR hastalarında kortikosteroid kullanımıyla ana şikayetlerindeki azalma yanında yaşam kalitesinde artışlar olduğu gözlenmiştir. Kortikosteroid tedavisinin etkili olması için en az 1 hafta kullanılması gerekir. İdeal olarak alerji mevsiminden ve alerjen maruziyetinden önce başlanmalıdır. En fazla etkinliği sürekli kullanımda gösterseler de ihtiyaç olduğu sürece, 2-4 hafta kadar kullanımı da faydalıdır.
AR gelişimindeki ana iki mekanizma (IgE sentezi ve mast hücre degranülasyonu) lokal kortikosteroid tedavisiyle engellenemez. Ancak kortikosteroidler T hücre çoğalmasını engeller; kemokin ve sitokin üretiminde, araşidonat metabolizmasında, eozinofil ve bazofillerin toplanmasında, mukus salgılanmasında, damar geçirgenliğinde azalma sağlar. Bu nedenle burun içi kortikosteroid kullanımı burunda eozinofil, mast hücre sayısında ve sitokin üretiminde azalma sağlar. Burun içi kortikosteroidlerin AR’ de bu kadar etkin olması patofizyolojide histamin dışı mekanizmaların da etkin olduğunun bir başka göstergesidir.
Piyasada birkaç burun içi kortikosteroid preperatı mevcuttur. Bunlar; doza, kullanım yaşına ve püskürtücüye göre değişkenlik gösterir. Yapılan çalışmalarda burun içi kortikosteroid çeşitlerinin birbirlerine üstünlüğü saptanmamıştır. Astımdaki klinik deneyimlerimize göre, eğer hasta bir burun içi kortikosteroide direnç gösterirse, daha güçlü bir kortikosteroide geçilebileceği öngörülür. Steroid preparatlarının hepsi etkili olan ilaçlardır; önemli olan hastaların bu ilacı uygun şekilde kullanmasıdır. İlaç seçimleri öncelikle hastaların tercihlerine göre yapılmalıdır.
Burun içi kortikosteroidlerin kullanımıyla oluşan yan etkiler ve ilacın sistemik emilimi hakkında, yeterli klinik veri yoktur. Burun içi kortikosteroidlerin biyoyararlanımıyla ilgili birkaç çalışma vardır. Hidrofobik özellik, lokal metabolizma, akciğer dokusundan emilimin olmaması nedeniyle, bu ilaçların burun mukozasından sistemik dolaşıma geçmeleri ve ciddi bir yan etki göstermeleri beklenmez.
Burun içi steroidler, orta-ağır klinik bulguları olan MAR ve PAR hastalarında ilk tedavi seçeneğini oluştururlar. Antihistaminik ve kortikosteroid kullanımı ile yapılan karşılaştırmalı çalışmalarda serum ve idrar kortizon seviyelerinde azalma ve ACTH stimülasyon testinde bozulma olmaz. Dolayısıyla ciddi bir kortizon yan etkisinden bahsetmek mümkün değildir. Burun içi kortikosteroidler lokal tahriş, ağızda acı tat, burunda kuruluk, burun kanaması gibi yan etkilere neden olabilirler. Yan etkiler ilacın formülasyonuna göre değişir. Sulu formlar aerosol formlara göre daha az yan etkilere neden olmaktadırlar.
İmmünoterapi
Çimen poleni, yabani ot poleni, kedi alerjeni, ev tozu akarlarının neden olduğu AR’ de uygulanan immünoterapi etkinliği üzerine sayısız kontrollü çalışma yapılmıştır. Şu an için modern tıbbi yöntemler arasında hastalığın kökenine yönelik ve kür sağlamaya (hastalığın altını kazımaya) aday tek tedavi modeli immünoterapidir. İmmünoterapi ile AR’ nin şiddeti ve hastanın ilaçlara olan ihtiyacı azalmaktadır. Hastanın yaşam kalitesinde iyileşme saptanır. AR’ li hastalarda alerjik astım gelişme riskini azalttığı gösterilmiştir; ayrıca yeni alerjen duyarlanma riskini de ortadan kaladırdığı bildirilmiştir. Ağır AR ve konjunktivitli, burun içi kortikosteroidlere cevap vermeyen hastalarda immünoterapi ile alerjen duyarlılığı 10 kat azaltılır. Böylece bu hastalarda belirtilerde ve ilaç kullanım miktarında azalma gerçekleşir. Yine alerjik astımlı hastalarda yapılan çalışmalarda immünoterapinin, belirtileri ve β agonist ilaç kullanım ihtiyacını azalttığı tespit edilmiştir. İmmünoterapinin etkinliği yeterli dozda alerjenin (~ 10-15 μg) yeterli süre uygulanmasına bağlıdır. Şu an klinik uygulamalarda kullanılan doz geçmişte kullanılana oranla çok daha fazladır.
İmmünoterapi öncelikle inatçı rinitli ve standart ilaçlarla karşı ciddi yan etki gösteren hastalara uygulanır. Burun içi kortikosteroidler tüm vücutta etkili olmadıkları ve belirtilerde tam iyileşme sağlayamadıkları için immünoterapi seçenek haline gelir. Burun içi kortikosteroidler güvenli olsa da bazı hastalar bu ilaçları kullanmak istememektedir. Hastaya immünoterapi uygulama kararı vermeden önce hastanın bir polen mevsiminde tam olarak polenlere maruz kalması gerekir. İmmünoterapi uzun süreli olarak bağışıklık sisteminde modülasyon sağlayan tek tedavidir, bu da immünoterapi için ayrı bir endikasyon oluşturur. Alerjenlerden korunma ve ilaç ile tedavi yöntemleri uygulandıkları sürece etkilidir. İmmünoterapinin etkinliği ise 3-5 yıl uygulandıktan sonra yaşam boyu devam eder.
5 yıl uygulanan immünoterapi ile ömür boyu uygulanan ilaç tedavisi karşılaştırılınca maddi avantajları ortaya çıkar. Bazı hastalar immünoterapiyi uzun dönemli bağışıklık sistemi modülasyonu sağladığı, belirtileri gerilettiği, günlük ilaç kullanımından kurtardığı için tercih ederler.
İmmünoterapi, ölümcül anafilaksi açısından küçük bir riske sahiptir (ABD’de 2 milyon immünoterapi tedavisi gören hasta içinde 3 ölümcül reaksiyon/yıl). Ölümcül anafilaktik reaksiyon riski nedeniyle immünoterapi deneyimli kişilerce (alerji ve immünoloji uzmanlarınca) acil müdahale olanaklarının bulunduğu kliniklerde uygulanmalıdır.
Bazı hastaların birden çok alerjene karşı hassasiyeti olabilir ve bu hastalara uygulanan eski immünoterapi protokollerine göre çoklu alerjenin, tekli alerjenler kadar etkili olamayacağı le ilgili görüşler vardı. Ancak son dönemde yapılan çalışmalar ve kullanılan immünoterapi materyallerinde konsantrasyon ve standardizasyon problemleri ortadan kaladırıldığı için çoklu alerjen immünoterapinin en az tekli alerjen immünoterapi kadar etkili olduğu bildirilmektedir. Maalesef immünoterapi mantarlar gibi antijenlere yeterli etkinlik göstermeyebilir.
Alerjik inflamasyonu azaltmak için bağışıklık sistemi yanıtı ile alakalı yeni tedavi yöntemleri araştırılmalıdır. Astım için antisitokin tedavilerinin de olduğu birçok deneysel tedavi geliştirilmiştir ve bu tedaviler AR için de etkili olabilmektedir.
Genelde AR hastaları için mevcut tedaviler yeterli olmaktadır. Burun belirtilerinin devam etmesi ve ilaçla tedavinin AR için yeterli olmadığı durumlarda rinitin diğer formları için ayırıcı tanı yapılmalı ya da sinüzit veya atipik migren varlığı araştırılmalıdır.
Sağlıklı Günler Dileğiyle…
Prof. Dr. Cengiz KIRMAZ
