To prepare a national guideline for Otorhinolaryngologist who treat allergic rhinitis patients.The study was conducted by three authors, namely the writing support team. The support team made the study plan, determined the writing instructions, chose the subgroups including the advisory committee, the advisors for authors and the authors. A workshop was organized at the very beginning to explain the details of the study to the team. Advisors took the chance to meet their coworkers in their subgroups and determined the main headings and subheadings of the guideline, together with the authors. After key words were determined by the authors, literature search was done in various databases. The authors keep in touch with the advisors and the advisors with the advisory committee and the support group at every stage of the study. National and International published articles as well as the abstracts of unpublished studies, imperatively presented in National Congresses, were included in this guideline. Only Guideline and meta-analyses published in last seven years (2013-2017) and randomized controlled studies published in last two years (2015-2017) were included. After all work was completed by the subgroups, support team brought all work together and edited the article.A detailed guideline about all aspects of allergic rhinitis was created.The authors believe that this guideline will enable a compact and up-to-date information on allergic rhinitis to healthcare professionals. This guideline is the first in the field of Otolaryngology in Turkey. It should be updated at regular intervals. Allergic rhinitis (AR) is a frequently seen global upper airway disorder affecting individuals at all ages. The upper airway is in continuum with a number of important regions, and disorders of upper airway cause significant comorbidities. The most frequent comorbidity of AR is asthma. Acute or chronic rhinosinusitis, otitis media with effusion, adenoid hypertrophy and gastroesophageal reflux may accompany AR. AR affects quality of life negatively since it is a frequent disease affecting individuals at all age groups, and may lead to complications.Although late diagnosis of AR or errors in its treatment do not lead to fatal outcomes in the early phase, they may result in significant morbidity. Errors in diagnosis and treatment result in an economic burden and psychological dysfunction in the affected patients. Therefore, its epidemiology, and the basic principles for avoidance, diagnosis, treatment and alternative treatment must be known.Physicians in various disciplines come across with AR patients due to high incidence and prevalence of disease in all age groups, and its relation and effect on multiple body systems. Not only allergists and pediatricians, but also otorhinolaryngologists frequently encounter with those patients. In Turkey, there are no Guideline prepared for all medical specialties. This guideline has been prepared to increase awareness of every physician at all disciplines and grades. It intends to give clear and practical messages on epidemiology, clinical picture, complications, and treatment of AR by transferring the experiences of the otorhinolaryngologists in Turkey.AR was first described by Hansel in 1929, based on its clinical symptoms, namely sneezing, nasal obstruction, and rhinorrhea. Allergic Rhinitis and its Impact on Asthma (ARIA) working group was founded by World Health Organization in 1999. This group has prepared detailed Guideline for clinicians on definition, classification, treatment algorithms using data in the literature, and updated them regularly , they are processed by epitope peptides, and presented to T-helper (Th) lymphocytes together with major histocompatibility (MHC) class II molecules. Activated CD4+ Th2 lymphocytes release cytokines, mainly interleukin (IL)-4 and IL-13, and they communicate with B cells which synthesize allergen-specific IgE (IgE sensitization). IgE releasing memory and plasma cells also develop. Then, the allergen specific IgE binds to the high-affinity IgE receptors on the surface of the mast cells , and cause eosinophil, Th2 lymphocyte and basophil infiltration into nasal mucosa. RANTES , eotaxin, monocyte chemoattractant protein (MCP)-4 and Thymus and activation regulated chemokine (TARC) are released, which provide a strong chemotaxis for eosinophil, basophil and T lymphocytes. Granulocyte-macrophage colony-stimulating factor (GM-CSF) increases the survival of eosinophils that have invaded the nasal mucosa. Eosinophilic cationic protein (ECP), thrombocyte activating factor and major basic protein released by eosinophils also play role in the late phase. Late phase response is particularly related to nasal congestion. Both upper and lower airways are affected by the local inflammation of AR, and systemic inflammation appears -a, RANTES, TARC, eotaxin, stem cell factor (SCF)] result in the allergic inflammation. Matrix metalloproteinase (MMP)-2, MMP-9 and MMP-13 are released from the nasal epithelial cells, and they degrade the extracellular matrix. Human Leukocyte Antigen – DR isotype (HLA-DR) and CD86 expressed by nasal epithelial cells present antigen to T cells. IL-25, IL-33 and Epithelial cell-thymic stromal lymphoprotein (TSLP) are important inducers of AR. IL-4 is produced by natural killer (NK) 1+ T and mast cells, and induces Th2 differentiation. IL-12 is produced by macrophages and NK cells, and causes Th1 differentiation. An increase in IL-25 accentuates Th2-related inflammation. IL-33 enhances Th2 response, and activates type 2 innate lymphoid cells (ILC) that release IL-5, IL-9 and IL-13. These three cytokines contribute augmented Th2 response and tissue eosinophilia by increasing ILC. The allergens tend to destruct the epithelial barrier in AR. Proteolytic enzymatic activity of various allergens directly activates the epithelial cells, cause cytokine-chemokine release, and result in airway inflammation, independent of IgE.Endothelial cell-derived VCAM-1 increases in the pollen season. RANTES and eotaxin are other important cytokine and chemokine released by the endothelial cells. H1 receptor is also expressed by the endothelial cells. Macrophage and dendritic cells (DC), too, release chemokines and influence Th2 cells as well as tissue fibroblasts. IL-4 induces allergic fibroblast proliferation, and GM-CSF production increases through histamine stimulation .Allergen tolerance may occur by induction of T regulatory (Treg) cells that balance the hyper-activation of the immune system . All proFOXP3+Treg and IL-10 positive Tr1 cells, which are two subunits of inducible Treg cells, play role in development of allergen tolerance . The mutTogether with other factors, it is evident that a decrease in Treg cells plays an important role in development of AR. CD4+CD25+Treg cell numbers decrease in vitro in patients with seasonal AR. In patients with persistent AR, the number and the functions of CD4+CD25+Treg cells are normal, however the number of IL-10 releasing Treg cells decrease , 9.The most important function of innate immune system in the upper airway is detection of the microorganisms. It is the host defense mechanism coded by the host genes. They include epithelium, mucus layer, cilia, soluble proteins, complement, defensin and a number of cytokines and chemokines. The Dcs, macrophages and mast cells in the upper airway contribute the process. There are two types of DCs: myeloid (mDC) and plasmocytoid (pDC). mDCs, are rich in microbial pattern recognizing receptors, which make a subepithelial network. pDCs express toll-like receptor (TLR)-7 and TLR-9, and release interferon alpha; they play a particular role in anti-viral response. Mast cells express complement receptors for TLR1, TLR2, TLR4,TLR6, C3a and C5a. Neutrophils and NK cells are crucial components of this system. First-line defense provided by innate immune system plays an important role in future development of tolerance or chronic inflammation.Antimicrobial peptides (AMP) kill microbes straight off. Cathelicidin is one of them, and it triggers tissue inflammation. Defensin is an antimicrobial against bacteria, viruses and fungi .Mast cells play a crucial role in the first phase response of AR. They are the main producers of histamine, leukotriens and prostoglandins. They also release cytokines and chemokines that regulate the late phase response. IgE-activated mast cells express vast amounts of high-affinity IgE receptors (FceRI), CD40L, IL-4 and IL-13. They stimulate local IgE synthesis in nasal mucosal B cells. Mast cells auto-activate themselves by IgE or IL-4 mediated FceRI upregulation. In this way, they intensify the ongoing inflammation .Th2 cells play a role in development and progress of cytokine-dependent inflammation. Basophils are present in the nasal lavage fluids of AR patients, and they are thought to be the main sources of histamine in the late phase reaction. Basophils are also important sources of LTC4 .They infiltrate the nasal mucosa in AR .Group 2 innate lymphoid cells (ILC2) release Th2 cytokines. They have been shown to be increased in the peripheral blood in cat antigen-related AR. Another study showed increased ILC2 in peripheral blood of the patients with pollen allergy, and their numbers decreased after subcutaneous immunotherapy .AR patients produce type 2 cytokines, and they have a high NK cytotoxic capacity (14). Those cells are giant granular lymphocytes. They produce cytokines such as Interferon- gamma, TNF-alpha and GM-CSF. They do not need MHC receptors to identify their target cells.They play a crucial role in the nasal mucosa. The number of eosinophils and the amount of ECP increase in parallel with the severity of the symptoms .The type and the amount of the allergens that come across with APC are important in an immunological reaction. The most significant APCs are the DCs . There aCD4 Th cells are formed by activation of DCs. These cells activate effector cells including eosinophils and neutrophils, and cause differentiation of B cells into plasma cells, releasing pathogen-specific immunoglobulin. Another specific T cell group, Tregs, inhibit the immune response. IL-10 and TGF- beta expressed by Treg cells inhibit activation of other T and B cells, DCs and mast cells , 20. OthCytokines are soluble proteins or peptides that play role as the mediator hormones of the immune system. Their functions may change in relation with the target cell. Chemokines are a subgroup of the cytokines, and they cause migration of leukocytes into the site of inflammation in AR. IL-1 and IL-2 cause B cell activation. IL-33, IL-25 and TSLP are released by nasal mucosal epithelial cells, and mediate uptake of the allergen by antigen presenting DCs. T-cell informing cytokines interact with undifferentiated T helper (CD4+) cells to induce different immune responses. IL-12 and interferon-gamma induce formation of type 1 Th1 cells which fight against bacteria and viruses. IL-4 pioneers Th2 cells that fight against the parasites. Th17 battles with bacterial and fungal infections, and plays role in autoimmune diseases. Treg cells induce release of IL-10 and transforming growth factor (TGF)-b , inhibit migration of the inflammatory cells, and suppress inflammation by reducing Th function . Th-effeChemokines induce cell chemotaxis. They define the type of migratory inflammatory leukocyte . Some chemokines induce high concentration of mediator release from leukocytes, and play role in allergic inflammation. The most crucial chemokines in allergic inflammation are eotaxin-1 (CCL11), eotaxin -2 (CCL24) and eotaxin-3 (CCL26). All of them exert their action through CCR3 receptors located on eosinophils, basophils and Th cells. Another crucial Th2 chemokin is RANTES (CCL5) acting through CCR5 receptor.In a small group of patients, serum specific IgE and skin prick tests are negative, however these patients have typical AR symptoms. Local IgE synthesis in the nasal mucosa has been presumed after identification of IL-4 and epsilon gene transcription in nasal mucosal B cells with in situ hybridization. Local IgE production may explain why some patients develop asthma and eczema and some others develop AR.Absence of AR symptoms in presence of positive serum specific IgE and skin prick test may be due to lack of local IgE. It has been noted that some of the patients diagnosed with non-allergic or idiopathic rhinitis might in fact have local IgE-dependent rhinitis . A nasalArachidonic acid is released from cell membrane phospholipids in cells activated by phospholipase A2. Arachidonic acid is metabolized through 5-lipoxygenase (5-LO) pathway into leukotriene (LT) B4 and cysteinyl leukotrienes (CysLT), namely, LTC4, LTD4 and LTE4. Neutrophils are the main sources of LTB4, on the other hand, mast cells, basophils and eosinophils produce mainly CysLT. CysLT play role in eosinophil migration, stimulation of airway mucus production, and upregulation of inflammatory cytokines. Prostaglandin (PG) E2, PGD2, PGF2alpha, prostacyclin and thromboxane (TXA2) are produced from arachidonic acid through cyclooxygenase (COX) pathway. Mast cells produce mainly PGD2. There are two forms of COX: basal (COX-1) and inducible (COX-2) forms. PGs have inflammatory functions , however they may act as anti-inflammatory endogenous molecules . Lipoxin (LX) A4 is produced by leukocytes from arachidonic acid through 15-LO pathway, or LTA4 is produced and metabolized into LXA4 in thrombocytes. Low LTE4 and PGD2 levels have been determined in nasal biopsy of the patients with AR. CysLT, LTB4 and PGD2 increases with nasal allergen provocation. Nasal symptoms improve with CysLT1 receptor antagonist treatment. LTA4 analogs have potential regulatory actions in inflammation of AR .Upper airway is the first barrier to allergens. The epithelial barrier of the nose and paranasal sinuses is composed of pseudostratified ciliated epithelium. The epithelial barrier contains antimicrobial proteins such as defensin, cathelicidin, lysosome and lactoferrin. S-100 proteins also have antimicrobial activity through innate immunity and Toll-like receptors . Tight jThe nasal epithelium is innervated by unmyelinated type C trigeminal nerve endings. Sympathetic neurons innervate the arteriovenous anastomoses of the venous sinusoids. Histamine stimulates H1 receptors. Nociceptive receptors are depolarized, resulting in itching in patients with AR. Calcitonin gene-related peptide (CGRP) is a potent vasodilator, and it is closely associated with neuromedin B and gastrin releasing peptide (GRP). Tachykinin, neurokinin A and substance P induce glandular exocytosis while glutamate is an excitatory amino acid neurotransmitter. Local CGRP release results in plasma exudation from the membrane vessels. The mediators such as leukotriene B4 and nerve growth factor induce expression of sensory receptors, neurotransmitters and inhibitory autoreceptors. Afferent receptor sensitivity is induced by an increased expression of endothelin and bradykinin receptors, transient receptor potential vanilloid 1 (TRPV1), purinergic P2X receptors and acid-sensing ion channel 3 (ASIC3). Damaged cells release potassium and calcium. The nociceptive neurons travel to pons, turn caudally at the trigeminal spinal pathway, and end at the dorsal horns of the caudal interneurons of the first three cervical segments. Glutamate and N-methyl-D-aspartic acid bind receptors and depolarize interneurons. GRP is the neurotransmitter of the itching neurons. They cross the midline to reach lateral trigeminothalamic tract, and end at the medial thalamus. Axonal branches travel to superior salivatory nucleus, and enrich parasympathetic reflex bilaterally. This reflex stimulates muscarinic M3 receptors, and glandular exocytosis and seromucous rhinorrhea are triggered. This mechanism explains the benefit of the patients from anticholinergic medications. Tertiary thalamic nerves transmit mucosal sensation to interoceptive cortex, situated at the posterior insula. The management of these perceptions is performed by the interactions in the brain, explaining the negative effect of AR on cognitive functions at school and work. Anterior insular efferent pathways activate brainstem sympathetic (right insula) and parasympathetic (left insula) stimulation .Continuance of allergic symptoms despite use of H1 histamine antagonists has led to research on other receptors. H4 histamine receptor plays role in immune regulation, and it is one of the main targets for treatment of AR. Specific H4 antagonists have been investigated by various researchers, however we do not have clear data on their clinical efficacy .A number of patients report that their symptoms are triggered not only by allergic stimulation, but also with non-specific stimuli including smoke, cold air and perfumes. Increased sensitivity of nasal mucosa to stimuli is called as nasal hyper-reactivity, and may be evident in patients with AR and non-allergic rhinitis. Nasal epithelial damage and increased permeability of the epithelium lead to stimulation of sensory nerve endings, resulting in mediator release from the mast cells. In addition, non-adrenergic non-cholinergic neurotransmitters  activate the cholinergic system that leads to nasal vasodilatation and increased secretion. Nasal hyper-reactivity may be tested with nasal provocation using cold-dry air .AR is a frequent disease affecting both adults and children. It is considered as a significant health problem due to its negative effects on school / work performance and quality of life as well as its high economic burden. The classification of AR is based on the subjective clinical symptoms of the disease. It is classified in relation with the severity (mild/moderate-severe) and duration (intermittent-persistent) of the symptoms.Apart from its frequency, AR is a significant health problem due to its economic burden, absenteeism and comorbidities, including bronchial asthma. Classification of AR is crucial since it can be confused with other types of rhinitis, its treatment plan is based on symptoms and duration of the disease, and a common language among physicians is needed to determine the benefit from therapy. AR may be classified in accordance with the time of exposure to allergen, and frequency and severity of the symptoms , 31. TraThis term is used for the disease that becomes symptomatic only in specific periods of the year, in presence of allergens in the environment. The responsible allergens are usually pollens. They are released into the air at the same time of year in regions with a moderate climate. Similarly, some mold spores increase in the summer, and cause seasonal symptoms in sensitive patients. The symptoms of some patients increase in cold seasons, and the responsible allergens may be indoor mold spores, house dust mites, and animal allergens, since their concentrations increase indoors when the inside temperature is high and windows are closed.Most of the patients have perennial symptoms. The responsible allergens may be animal fur, house dust mites and the spores of the indoor molds. The diagnosis and treatment of these patients is complicated in presence of a non-allergic rhinitis causing chronic nasal congestion.In this form of AR, the symptoms appear occasionally. Appearance of symptoms in contact with a cat in an individual with hypersensitivity to cat allergen may be an example. Another example may be becoming symptomatic after housecleaning in case of house dust mite hypersensitivity. A detailed history may help the diagnosis in this form of AR.These patients are sensitive to perennial allergens. Their symptoms exacerbate in relation with the periodical increase in the allergenic load , 31.Traditional classification AR is not practical in many patients since most of the patients have multi-sensitivity to seasonal and perennial allergens. Therefore, ARIA working group of World Health Organization proposed a new classification of AR . In thisThe term “intermittent rhinitis” indicates duration of the symptoms less than 4 days/week, or less than 4 consecutive weeks/year.The term “persistent rhinitis” indicates presence of symptoms more than 4 days/week and more than 4 consecutive weeks/year. These patients usually have symptoms every day of the year.AR is classified as “mild” or “moderate/severe” in relation with the severity of the symptoms.In this form of the disease, the patient has mild symptoms not influencing sleep, school or work performance, or sportive or daily activities.This is the form of disease in which the symptoms have negative influence on sleep, school/work, leisure, or daily activities.In the light of aforementioned information, AR may be classified into four groups as “mild intermittent”, moderate/severe intermittent”, “mild persistent” or moderate/severe persistent” in relation with the duration and the severity of the symptoms .This term is used for the patients who have classical AR symptoms in absence of systemic atopy, ie. negative skin tests and serum specific IgE . Most ofth more frequently diagnosed disorder in the outpatient clinics in the USA. It ranks as the 5th most frequent chronic disease in the adults, and the first most frequent chronic disease in the children in the USA  in the USA revealed presence of AR symptoms in one of three individuals in the previous year, independent of an upper respiratory tract infection. There was hypersensitivity for at least one allergen in 52.7% of the participants. Global prevalence of AR has been estimated as 10-20% .AR prevalence shows regional differences. The prevalence in adults has been reported as 16.3% in the Switzerland while it has been reported as 23.5% in the USA . “The InThere are only a few studies on AR prevalence in our country, and further studies on larger populations are needed. A multi-center study on 4125 individuals  from every geographical region of Turkey was conducted in 44 centers. AR prevalence was found as 22.3% in adult men, and as 23.8% in adult women . A studyAlthough the data are insufficient, the results of the Turkish studies indicate various differences between Turkish population and the populations of other countries. Further studies on larger populations are needed in Turkey.AR prevalence demonstrates regional differences in the world. The prevalence has been reported as 25% in Europe, however there are differences among the European countries. AR prevalence was reported as 28.5% in Belgium, 24.5% in France, 20.6% in Germany, 16.9% in Italy, and 26% in the United Kingdom . A studyPediatric AR prevalence has been reported as 13-19% in the USA . A largeAR prevalence shows differences in our country in accordance with geographical regions, diet and lifestyle. A study that included 11,483 participants in İstanbul investigated AR prevalence in 6-7 -year-old schoolchildren, and reported once-in-a-lifetime AR prevalence as 44.3%, active AR prevalence as 29.2% and physician-diagnosed AR prevalence as 8.1% . A studyA number of factors may affect AR prevalence. A study that investigated AR prevalence in accordance with the age groups designated the age groups as 20-44, 45-64 and 65-84 years, and found the prevalence as 26.2% in females and 28.6% in males in 20-44-year group, as 21.3% in females and 19.8% in males in 45-64-year group, and as 17.8% in females and 17.1% in males in 65- 84-year group. The authors also reported lower AR prevalence in smoking individuals, and higher prevalence as level of education increases and socio-economic status gets better . A meta-A large-scale study from China reported AR prevalence as 13.5% in rural, and as 19.1% in urban areas. The AR prevalence was significantly higher in the urban areas . A studyA total of 304 individuals were tested for house dust mite allergens, and AR was found in 46%, non-allergic rhinitis was found in 50%, and LAR was seen in 4% . An AustThe children exposed to air pollution and high carbon monoxide in the city in their first year of life were reported to have higher AR prevalence at 6-7 years of age . A studyIt was reported that children with 25-OH levels greater than 75 had lower AR prevalence compared to children that had 25-OH levels lower than 50 . A largeAR classification is based on clinical subjective symptoms. In ARIA classification, AR is classified as “intermittent” if the duration of the symptoms is less than 4 days/week, or less than 4 consecutive weeks/year, and as “persistent” in presence of symptoms more than 4 days/week and more than 4 consecutive weeks/year. AR is classified as “mild” or “moderate/severe” in relation of the symptoms’ influence on the quality of life . Since tAcoustic rhinometry and rhinomanometry that measures nasal obstruction, nasal nitric oxide determination to assess inflammation, and visual analog scale (VAS) that defines symptom severity are used to determine the clinical severity of AR symptoms. It has been claimed that VAS was comparable with the quality of life scales designed for AR for quantitative measurement of severity of AR . VAS hasAlthough quantitative data collection by visualization through VAS helps the clinicians for the analysis of the symptom scores, this inventory is not sufficient to determine the comorbidities of the disease and to convert them into data. In this context, quality of life scales provide a standardized and numerical summary of the symptoms of the patient, and functional and psychosocial results of the disease and its treatment, and epidemiological analysis of the data is made possible. General quality of life scales provide data for an overall functional disability and disturbance, therefore they can be used for all segments of the population, for all diseases and disorders, and for various medical interventions. Disease-specific quality of life scales are specific scales for the disease under research, and may detect small variations .This is an overall health questionnaire used for detecting the effects of chronic conditions on functional heath status . The oveThis is a frequently used 18-item questionnaire directed to overall, physical and social benefits of the treatment employed. It is mostly used in studies on hearing surgery and hearing aids .This scale consists of the questions on nasal symptoms. It measures the severity of the symptoms as well as the emotional and mental significance of these symptoms for the patients. Symptom-related comorbidities are also included. SNOT-22 includes additional symptoms, it is proven to be reliable and valid, and it is an easy-to-use, popular scale used frequently in studies on rhinitis symptoms in order to obtain quantitative data .It is the most frequently used rhinitis-specific quality of life scale . It measThe target population of this questionnaire is the asthma patients with comorbid AR. It has been proven to be reliable in patients with simple rhinitis and comorbid allergic asthma . Since tThis is a 30-item questionnaire for all rhinology patients. It measures quality of life in patients with any nasal disorder .It is a specific scale for children with persistent sinonasal symptoms. It has been used in treatment and follow up of pediatric sinonasal disorders.This scale is used to follow up the rhinitis symptoms after treatment. Higher scores in follow up has a significant correlation with disease control.This is a nasal symptom assessment questionnaire used in adults. It is a reliable and valid 5-item nasal symptom scale that assesses nasal obstruction . Its valThis is a disease-specific questionnaire that measures the impact of the symptoms on daily activities, and their functional and emotional effects. It has been found beneficial in AR patients as well as rhinosinusitis patients .This scale includes major and minor symptoms of rhinosinusitis.Rhinoconjunctivitis quality of life questionnaire has been regarded as the main reliable and valid distinguishing scale for rhinitis-related quality of life . Other tThe studies on the impact of AR on quality of life usually employ the aforementioned scales. A meta-analysis compared house dust mite-related perennial AR and pollen-related seasonal AR in 2016 . IncludeA detailed history is crucial in AR since nasal inflammation may occur in a number of disorders. Rhinitis symptoms are similar in allergic and non-allergic rhinitis. Therefore, the specific points for AR in the history may help the physician in the diagnosis of AR.Rhinorrhea, nasal itching, sneezing and nasal congestion are the main symptoms of AR. Rhinitis is accompanied by eye, ear and throat symptoms. Rhinorrhea is usually copious and serous in character. Sinusitis may be evident in some patients. In this case, the patients may complain of purulent nasal and postnasal discharge, pressure on face, anosmia, headache and halitosis . Nasal iMost of the AR patients complain of nasal congestion that worsens at night. Rhinorrhea, nasal itching and sneezing are mostly seen in seasonal AR, however nasal congestion is frequently evident in perennial AR. Nasal congestion may result in mouth-breathing and snoring . There aThe patients should also be questioned for the most bothersome symptom since the main symptom is important in treatment planning.Except for the main symptoms, the patients with AR may have other symptoms due to the systemic effects of the allergic inflammation, or presence of comorbid diseases.Itching of palate and/or ear, postnasal dripping and dry cough are frequently seen in patients with AR. Smell and taste problems may also be evident .Itching and watering eyes, eye redness and photophobia usually appears in pollen-related AR. Nasolacrimal canal obstruction due to nasal congestion contributes the severity of the ocular symptoms. Compared to non-allergic rhinitis, ocular symptoms are more prominent in AR .It has been claimed that AR is a risk factor for otitis media with effusion. In this case, hearing loss, ear fullness and otalgia may be evident .Paroxysmal dyspnea, wheezing and cough may appear in case of comorbid bronchial asthma .“Oral allergy syndrome” or “pollen-food allergy syndrome” is a kind of food allergy characterized by itching at the mouth and throat, and it is due to cross-reaction of pollens with uncooked fruits and vegetables, various spices and nuts .AR patients may have symptoms including malaise, fatigue and somnolence due to nonspecific systemic effects of the allergic inflammation. These symptoms may also be due to impaired sleep as a result of nasal congestion. Impaired sleep and rhinitis symptoms may lead to impairment of concentration which has a negative impact on school or work performance. Itchy skin may also be a symptom, particularly in the individuals with pollen hypersensitivity .Appearance of symptoms after getting in contact with the allergen is a characteristic of AR in hypersensitive individuals. Therefore, the patient should be questioned whether his/her symptoms appear at outdoors, home, workplace, or in contact with a pet.Determining the time of the year when the symptoms arise, and whether they are seasonal or perennial is important both for diagnosis and treatment planning. Seasonal AR usually appears when the pollens are in the air. Perennial symptoms suggest that the responsible allergens are present in indoors, such as house dust mites. The symptoms may change and their severity may fluctuate in perennial AR. The duration of symptoms, and their persistence through the days in a week is important for differential diagnosis. AR symptoms usually persist for hours and days .The age of the patient at the time of onset of the symptoms is also important for the differential diagnosis. In most of the cases, the onset of AR symptoms is at adolescence or young adulthood. Non-allergic etiology should be taken into account if the symptom onset is after 40 years of age .After ascertaining the symptoms, determining and noting the severity of the symptoms is important in the follow up. The symptoms are regarded as mild if they do not have an impact on the quality of life, however in case of a negative impact on the quality of life  AR is regarded as severe .The patients with AR may have nasal hyper-reactivity similar to bronchial hyper-reactivity, and become symptomatic when exposed to non-allergenic materials including cigarette smoke, perfumes, detergents, various chemicals, air pollution, temperature/humidity alterations and cold air .The characteristics of the workplace, the equipment used, and the exposed agents should be questioned. A study on different occupational groups in Turkey reported that the allergic disorders mostly affected the ones working in textile, dye and chemistry industries as well as the ones working in an office . In anotThe patient should be questioned whether he/she was administered any medications for his/her symptoms, used them properly and regularly, and got any benefit from treatment, since all those are important for supporting the diagnosis and planning the treatment.The patient should be questioned for use of any medicines for any other medical conditions.The use of medications that may induce rhinitis  should be questioned by mentioning them individually. The correlation of the time of onset of the symptoms and the time to start the medication should be noted.The history of previous nasal surgery is of importance to appreciate the conditions that may cause similar symptoms.The patients should be questioned for presence of any chronic disorders including hypothyroidism , asthma,Some studies reported that passive smoking increased AR risk , 105, hoA number of studies investigated the effect of air pollution on AR development. Some reported that air pollution was correlated with AR development , 106-108Exhaust fume may cause atopic sensitization and AR. Diesel motors have been claimed to be more detrimental since they yield more particles .The household characteristics may play role in development of allergies. Living in a slum and use of fossil fuel and biogas have been claimed to increase the risk, however use of wood/coal burning stoves did not . It was The patient should be questioned for presence of a garden in his/her house. In case of living in an apartment, the floor at which the house located is of importance.The protective measures at household  should be questioned.Having pets is common particularly in the cities. Although the furs of the cats and dogs act as reservoirs for allergens, the allergen sources are their glands, saliva and urine. The allergens may remain in the household for weeks and even for months. A number of researchers investigated the relation of animal allergens and AR, however the results were conflicting. It was reported that early exposure to animals was protective for AR, this was a risk factor for AR, or did not affect AR development , 114-117Hypersensitivity to food allergens during pregnancy or early childhood has been correlated with AR development . It was AR prevalence was lower in children with older siblings and the ones living with large families .The household at infancy has been claimed to affect AR development. Moving into a new house may increase the risk for AR. It was reported that increased risk might be related to new chemicals . AR riskThe results of the studies on socioeconomic status and AR development are controversial. Although most of the studies claimed that high socioeconomic status was correlated with AR, some others claimed the opposite . The datHigh humidity has been shown to increase AR occurrence .Some factors during prenatal and postnatal periods and pregnancy may play role in AR development. Excessive exposure to allergens during pregnancy and use of oral contraceptives have been claimed to increase AR risk in the offspring. Use of proton pump inhibitors, H2 receptor blockers, antibiotics and paracetamol may also increase AR risk in the offspring , 127. CoAR risk was found higher in the ones that were born with a Cesarean section, and it was claimed that the baby was more susceptible to food allergens and aeroallergens since it was not exposed to vaginal flora during birth .Some studies concluded that hospitalization in the neonatal period, neonatal jaundice and phototherapy increased AR risk .Feeding the baby with mother’s milk was reported to avoid AR. Meta-analyses showed that the babies fed with mother’s milk developed AR less frequently later in life , 132.The studies that investigated the correlation of AR with exposure to house dust mites in prenatal period or early childhood reported conflicting results. Most of them did not correlate AR with exposure to mites early in life . Most ofUpper airway infection and sinusitis in childhood were claimed as risk factors for AR .There is a familial tendency for AR. Approximately 59% of the allergic patients have positive family history. The risk of developing an allergic disease in the child is approximately 47% if both parents are atopic. This risk is 13% if none of the parents are atopic, and approximately 29% if one of the parents is atopic. The risk of developing AR is 4-6 times more if the individual is asthmatic , 135. FaKeywords: Rhinitis, Allergic. Physical examinationThere are no specific nasal findings for AR. Otoscope, nasal speculum, and rigid and flexible endoscopes may be used for nasal examination .The patients with AR may have mouth breathing, sniffles, hypernasality and allergic salute, i.e. wiping and/or rubbing the nose in an upwards or transverse manner with the palm. A horizontal supratip crease may appear over the nose as a result of allergic salute .Nasal examination may be normal when there is no seasonal allergen exposure. Thin and colorless rhinorrhea, mucosal edema of the turbinates, serous secretion extending between the lower turbinate and nasal septum, purplish or pale nasal mucous membranes, and maceration at the nasal vestibule may be seen on nasal examination -140. NasChronic spasm of the Muller muscle due to venous stasis and hypoxia may head to horizontal lines, called as Dennie–Morgan lines on the lower eyelid. In addition, “allergic shiners” may be evident in the lower eyelid. Allergic shiners refers to hyperpigmentation of the lower eyelid skin, appearing as dark circles. The reason for this finding is disruption of venous blood flow in the periorbital region due to nasal mucosal congestion, pooling of blood around the eyes, capillary leak, and subcutaneous deposition of hemosiderin. Sclera may get thicker due to increased vascularity of the conjunctiva. Increase in ocular secretions, conjunctivitis, thinning of eyelashes, and scaling of the eyelashes may be evident , 141.Eczematous appearance of the external ear canal, postnasal discharge, hypertrophy of tonsils and lateral pharyngeal bands, posterior pharyngeal erythema and edema, granular oropharyngeal pharyngitis due to irritation of postnasal discharge, and vocal cord edema may be seen , 142. AdAR may lead to physical and mental complications particularly in children. Otitis media with effusion may occur in the short term, however chronic rhinosinusitis, asthma, orthodontic malocclusions, nasal polyposis and obstructive sleep apnea syndrome may be evident in the long term as physical complications. Mental complications include impairment of school performance and hyperactivity , 144. An international literature search was performed with the keywords “allergic rhinitis, in vivo testing and diagnostic testing” in Pubmed, Scopus, Google academic and Thomson Reuters databases. Only reviews and meta-analyses were taken into account until 2008 (7 publications). All publications on in vivo testing for AR have been included between 2008 and 2018 (156 publications). The abstracts were reviewed to eliminate the ones that were not directly on in vivo tests or diagnostic tests, and a total of 45 publications were reviewed. At the end, a total of 52 international publications were included in the study. National literature search was done on Ulakbim and Google academic databases with the keywords “alerjik rinit, in vivo testler, tanı testleri”, without any time limit.There are three types of in vivo skin tests used in the diagnosis of AR:1. Skin prick testing (SPT): This is the primary test for the diagnosis of IgE-mediated allergy. It has been frequently employed. Although very low, it may lead to severe complications. It provides valuable information if done and interpreted correctly.2. Intradermal testing (IDT): Used in the diagnosis of both IgE-mediated and delayed-type hypersensitivity reactions. Its complication rate is higher if used for the diagnosis of immediate, namely, IgE-mediated allergy, therefore its technique and interpretation necessitates expertise.3. Patch testing: Used for the other forms of delayed hypersensitivity, including contact dermatitis. It is primarily performed by dermatologists and some immunologists. This test will not be discussed herein since its role is limited in the diagnosis of AR.4. Scratch test: This test is not performed anymore.SPT provides information on presence of specific IgE against peptide antigens . It is based on application of a small amount of allergen into epidermis and avascular dermis to enable reaction with the specific IgE binded on the cutaneous mast cells. Histamine and other mediators released from the mast cells give rise to a visible “erythema and induration” skin reaction 15 minutes after the application of allergen.The quality of the test results depends on some steps, as follows :• The relevance of the used allergen with the investigated allergic condition• Application of sufficient amount of natural allergen into the skin in the correct manner• The functional status of the cutaneous mast cells• Correct interpretation of the result in the context of positive and negative controlsWhen performed correctly, SPT has high specificity and sensitivity for determination of allergen specific IgE. It may sometimes be more sensitive than in vitro specific IgE testing . It doesIDT is primarily used in the diagnosis of venom allergy and IgE-mediated drug allergy, particularly penicillin hypersensitivity, and its use requires more knowledge and expertise. It carries a higher risk for anaphylaxis compared to SPT, and it is usually performed in a hospital .AR diagnosis is based on patient history, clinical examination, and SPT or in vivo testing of serum for specific IgE. In case of any uncertainty in the diagnosis, other tests may be employed taking non-allergic conditions into account .SPT has various advantages since it is a fast and cheap test, and it provides a visual result for the patient. It should be a routine test for atopic individuals in whom the responsible allergen needs to be determined. SPT should not be used in the patients with dermographism or eczema, as well as in the ones who are on histamine-receptor-blocking medications . In this case, in vitro tests should be preferred. Skin tests performed using standardized inhalant allergens are quite safe.Indications for SPT are listed below:• Rhinitis / rhinoconjunctivitis / rhinosinusitis / allergic conjunctivitis• Asthma• Atopic dermatitis• Food allergy causing anaphylaxis, urticaria or acute eczema• Suspicion for latex allergy• Allergic bronchopulmonary aspergillosis, eosinophilic esophagitisSelection of the allergens depends on the condition to be diagnosed, and the risks for exposure to potential allergens. SPT is not recommended in conditions in which low-molecular-weight substances are thought to be responsible for allergy. These conditions include allergy for food additives, non-allergic adverse reactions of medicines, airway irritants, and most of the occupational allergies (the details will be discussed later).Indications for IDT are listed below:• Venom allergy• Immediate allergic reaction due to beta-lactam antibiotics and medicines with a valid protocol• Immediate allergy due to vaccinesIDT should be performed by a health professional with sufficient knowledge and expertise. IDT is not indicated for aeroallergens, and contraindicated for routine diagnosis of food allergy .Allergy tests have been shown to improve the accuracy of the diagnosis when the results are anticipated together with patient history . They arAllergy testing makes allergen avoidance, realistic use of medicines, and allergen immunotherapy possible in some cases. SPT is strongly recommended when the physician finds strong evidence for the benefit of allergen avoidance or allergen immunotherapy.SPT may also be employed for epidemiological research or determination of atopy not related with specific disorders.Although there is no age limit for SPT, one should consider that children and elderly have less skin sensitivity, and interpretation of the results is hard in this case. Babies usually have smaller indurations and larger induration reactions. Rarely, systemic side effects may appear in children (as occurs at every age). Experienced specialists should perform SPT to children younger than 2 years of age due to higher risk for complications and interpretation difficulties .Contraindications for SPT are :• Dermatological disorders at the possible sites to be used for SPT • Severe dermographism• Poor patient compliance• The patients who cannot stop antihistamines or other medicines that may affect the test resultsThese relative contraindications may be related to physical conditions of the place where test is performed, or the health professional that performs the test .:• Severe persistent or unstable asthma• Pregnancy • Babies and infants• The patients on beta blockersAppendix 1). First generation antihistamines usually change the skin response for a relatively short time, however second generation antihistamines change it for a longer time. So that the antihistamines should be stopped 10 days before a skin prick test. The suppression of skin test result shows differences among the members of the same class of medicines, and also among the patients. Tricyclic antidepressants, such as doxepin, have antihistamine activity, and should be stopped 1-2 weeks before the test  are some examples .Presence of some disorders may decrease shin sensitivity: chronic renal failure, cerebrovascular disorders, malignancy, spinal cord injury, diabetic neuropathy, and recent anaphylaxis. The SPT should not be performed on the extremities with lymphedema, paralysis or neurogenic disorders .Some recent studies reported that respiratory syncytial virus infections increased histamine release, and false positive skin test results might be obtained in the patients infected with this virus. Therefore, the test results should be interpreted carefully in presence of an acute viral infection .The allergens are injected intradermal to produce a small swelling in the skin. The increase in the size of the induration is examined 20 minutes after the injection. The injected allergens should be diluted 100 – 1000 fold compared to the concentration used in SPT. Using a correct injection technique and a proper interpretation of the result are important. The tester should keep systemic reaction risk in mind, including anaphylaxis. The risk is higher than SPT, although rare . IDT shoIDT is contraindicated for the diagnosis of food allergy, and its benefit is limited in case of allergies caused by inhalant allergens, due to its low specificity , 159. SPThese allergen extracts are produced specifically for SPT. They are aqueous solutions of the protein extracts obtained from the allergens, and 50% glycerol is added as a preservative. Therefore, they are quite viscous. They are sold in small bottles with a dropper.The commercial allergen extracts for SPT are not produced in Turkey. There are only a few international producer and retailers. The allergen extracts used in our country are produced by Hollister-Stier (USA), Stallergenes (Europe) and ALK-Abello (Europe and USA).The commercial allergen extracts should contain all allergenic proteins labeled on the bottle. However, they should not contain any allergenic proteins that cause a cross-reaction. For example, the allergen extract of one plant pollen should not be contaminated with the pollen of another plant. Some allergen extracts contain a mixture of the allergens, and this is labeled on the bottle. Examples may be the pollens of various grasses in one bottle, the pollens of various trees in one bottle, or different Alternaria allergens in one bottle.Some allergenic extracts have standardized allergenic potencies, while some others are prepared in regard to the weight of the allergen.Allergen extracts are complex mixtures. They contain a series of allergen proteins separated by electrophoresis, and visualized by immunoblotting. The extracts of different companies may contain different amounts of major allergen. This is why the products of different companies may produce different SPT results. This is also the main reason for obtaining different results with SPT and serum specific IgE measurement. Before interpreting the results of the studies, one should take whether the investigators used standardized extracts in the study .Allergenic substances contain hundreds of different proteins with unique designs. Only a subgroup of these proteins have allergenic potential. However, individuals may produce IgE for different proteins in the allergenic material. If the protein in the test material does not have the same protein sequence with the allergen that induced IgE in this individual (due to production process or protein instability), the test will give a false negative result although the patient has allergy. The aforementioned entity is a potential reason for a false negative SPT .Cross reaction is an important concept while choosing the allergen extracts for SPT and interpreting the test results. Cross reaction refers to reactivity of a specific IgE to a similar allergen, other than its specific allergen. The patient may have not ever been exposed to the second, similar allergen. Cross-reactivity of pollen and other allergens is mostly related to phylogenity, but there are also some biologically unpredictable models of cross-reactivity due to proteins that have conserved their structures across various species .The allergen test panel should be relevant to the clinical picture of the patient as well as the allergenic exposure. The number of the allergens in the panel should be kept at minimum, just sufficient for the diagnosis and treatment. Allergen panels with a relatively small number of allergens  are considered as adequate. However, a detailed test with more allergens may be needed if allergen immunotherapy is an option, or allergy for a rare substance is explored. The test panels must be prepared in accordance with the flora and fauna of the region . On the We suggest you to take pollen map of Turkey into consideration as well as the pollen calendar before planning an inhalant test panel in your center .SPT may be used to test IgE-mediated food allergy, however interpretation of the results is difficult. The test results may be positive, however no clinical correlation may be evident. This may be due to various factors, on the other hand, the test may be negative in presence of positive clinical findings . The anaThe constituents of the allergen extracts should be clearly labeled on the bottle. They are usually sold in a bottle with a dropper. The allergens are proteins in nature, therefore they need a refrigerated transport, and should be stored in the refrigerator. Their expiration date should be checked before use. Precautions should be taken to avoid bacterial contamination of the extracts as well as cross-contamination between the allergen bottles.The practical measures listed below are recommended:• Number the test bottles and align them in a row over a shelf• Open only one bottle when performing SPT. If you place the dropper over another bottle, the allergens cross-contaminate. In this case, the bottle and the dropper should be discarded• In order to avoid bacterial contamination of the tip of the dropper, cleanse the skin surface with alcohol. Apply the test only on the normal, healthy skin. While dropping the allergen extract on the skin, do not let the tip of the dropper touch the skin; however, the extract drop may touch the skinSome patients may have dermographism, and an induration may appear just by pricking the skin, even if an allergen is not used. This may lead to misinterpretation of the test result, and a false positive SPT. The negative and positive controls should be examined very carefully in this case. If the indurations of the negative and positive controls are equal, the test result cannot be interpreted. On the other hand, if the negative control is bigger than the positive control, the allergen results should be interpreted by comparing the allergen’s induration with the negative control. As an example, if negative control’s induration is 3 mm, the allergen indurations bigger than 6 mm should be regarded as positive. Since dermographism response may be inconsistent in different regions of the body, and false positive SPT results may occur, the tester should be careful while interpreting the results. The test should be regarded as “invalid” if the induration of the negative control is bigger than 3 mm. A delicate pricking technique may minimize the nonspecific reaction in patients with dermographism.Appendix 1), or a nonreactive skin should be considered if the erythema / induration size is smaller than 7 mm. SPT is not valid in this case. An erythema / induration ≥4 mm in the positive control is an acceptable result (or an erythema / induration 4 mm larger than that of negative control). The test is regarded as invalid if the induration of positive control is smaller than 4 mm.The positive control should produce an erythema / induration sizing approximately 7 mm. Use of antihistamines or other medications with antihistamine activity . Negative controls of SPT extracts are commercially available. The positive control may contain histamine , or codeine .For SPT the skin is pricked using a sharp lancet through the allergen extract for penetration of the allergen into the epidermis and superficial dermis. The skin may be pricked by a lancet or special applicators. The special applicators are designed to apply 5 or 8 allergens at the same time. The applicator is first submerged into the allergen extract, then applied over the skin to prick it. Lancet technique is used more frequently. In this technique, after the allergen extract is dropped on the skin, then the skin is pricked through the extract with a lancet. The skin should not be over-pricked with the lancet in order to avoid bleeding. A new lancet should be used for each allergen extract in order to avoid mixing of the allergens , 174.Appendix 6.3.7.4.A summary of the minimal and optimal requirements in SPT, circumstances that requires experience, and contraindications are given in The equipment needed for SPT is listed below ;• Allergen extract• Positive and negative control solutions• Sterile lancets for pricking the skin• A “sharp medical waste container” to dispose the lancets• A pen to mark the skin• A ruler to measure the sizes of the skin reactions• Test reportThe patient sits in an armchair. The arms of the patient should be in a suitable position for the tester. The patient is informed about the procedure (an informed consent form may be used). The test region is cleansed.The most suitable and frequently used part of the body is the plantar surface of the forearm, or the dorsal surface of the upper arm. The test region should be 5 cm superior to the wrist, and 3 cm inferior the antecubital fossa . Skin prAlthough skin cleansing with alcohol before SPT is not obligatory, it is recommended . The sites of the allergen extract drops are marked with a pen before dropping them. The drops should be at least 2 cm away from each other in order to avoid false positive results and overlapping erythema / induration reactions . If a muThe skin reaction of positive control, i.e. histamine, reaches its maximum size approximately 10 minutes after application, however the skin reactions for the allergens take 15 minutes to reach their maximum sizes. Therefore, it has been recommended to evaluate SPT results 15 minutes after application of the test material .The skin reactions of some allergens may enlarge up to 20 minutes. If test evaluation is done after 20 minutes, both histamine and allergen skin reactions may diminish, and a re-test may be needed. The test is evaluated and reported if the reaction of the positive control is bigger than the negative control, and/or positive control’s induration is bigger than 3 mm. The positive control’s skin reaction is usually measured as 7-9 mm.2  show a clear discrepancy.The size of the skin reaction should be recorded by the name of the allergen on the report. The reaction size may be noted in millimeters, or graded as +, ++, +++ or ++++. These two methods are widely used in the clinical practice. This subject is detailed in section 6.3.3.5.Itching due to allergen reactions may irritate the patient after SPT. The allergen extract should be cleansed with alcohol at the end of the test unless there is a contraindication for use of alcohol . Itching usually lessens in 15 minutes. Topical crèmes or cold application may decrease itching. Topical corticosteroids are not beneficial . Oral anIt is recommended to keep patients under supervision after the test, due to risk of systemic reactions, although rare . This suSPT report should be clear and understandable for other physicians. The SPT report should cover the following:• The name, address and correspondence of the physician• The name and date of birth of the patient• Date• The body region where SPT is applied • The name of the allergen applied • Negative and positive controls• The size of the reaction for every allergenThe longest diameter of the allergen reaction and the diameter perpendicular to this line are measured, summed up, and the mean of them is written on the SPT report. The induration and erythema diameters are measured with a transparent, flexible ruler.The SPT results may be reported between 0 and 4+ in accordance with the diameter of the allergic induration:• < 3 mm: (-)• 3-5 mm: (+)• 5-7 mm: (++)• 7-9 mm: (+++)• ≥10 mm: (++++)The reaction size of allergen may be compared to the reaction size of histamine for reporting purposes :• Induration diameter is smaller than half of induration diameter of histamine: (+)• Induration diameter is equal to half of the diameter of histamine’s induration: (++)• Induration diameter is equal to the diameter of histamine’s induration: (+++)• Induration diameter is 1.5 fold of the diameter of histamine’s induration: (++++)The patient’s life style, diet, and even occupation may need modifications in accordance with the SPT results. A long-term treatment or expensive allergen avoidance measures may be founded on these results. Therefore, the physician should meticulously examine the allergen reactions, take other clinical factors into account, and interpret the SPT carefully.The SPT results should be interpreted by taking the history, signs, and allergen exposure of the patient into account. In the presence of an allergic disorder (such as the ones listed in section 6.1), the physician may consider the positive allergen in SPT is associated with the symptoms if this allergen is related to the patient’s allergen exposure, and the symptoms flare up with exposure to this allergen, as mentioned in the history of the patient. Any SPT result uncorrelated with patient history should be handled with suspicion.SPT is a quite accurate and specific test for detection of allergen-specific IgE when performed correctly. On the other hand, presence of an allergen-specific IgE does not prove clinical reactivity of an individual to this specific allergen. Generally speaking, a bigger allergen reaction in SPT predicts a greater reaction to this allergen on exposure, but not the symptom severity . It has A positive SPT indicates presence of specific IgE. On the other hand, exposure to that allergen may not induce symptoms. This is called as “clinically silent hypersensitivity” or “clinically false positive test result” . The size of the SPT reaction may correlate with probability of the clinical reactivity to that allergen . In concA positive SPT does not predict the nature of the allergic symptoms. Various individuals with a positive reaction to the same allergen may present with different symptoms on exposure to that allergen.SPT may be negative due to insufficient allergenic protein content of some allergenic extracts, even if the patient has specific IgE. Negative SPT result does not rule out development of an allergic disorder in the future.Technical or tester-related mistakes may also lead to false positive and false negative SPTs. In this context, one should keep in mind that a false positive or false negative test result cannot be reproduced in an individual on re-testing.SPT is not used in the diagnosis of a non-IgE-mediated allergic disorder or intolerance. It is clear in some individuals that the adverse reaction is not mediated by a type 1 (IgE mediated) allergy. Other mechanisms should be considered in case of an adverse reaction in history, and a negative skin test.Every test has its own “performance characteristics” with regard to sensitivity, specificity, and positive and negative predictive values.The studies that investigated diagnostic value of SPT have shown different evidence levels. Common limitations of those studies bias in choosing the study group, absence of a suitable gold standard method, and lack of blinding. In SPT, allergen reactions and their sizes may vary when different commercial allergen extracts are used, and the test is repeated in the same individual .The specificity and sensitivity of SPT has been reported as 70-95% and 80-97%, respectively, for the diagnosis of inhalant allergy. The positive predictive value of patient history alone is 77% in the diagnosis of persistent allergic rhinitis, however this value increases to 97-99% when a SPT is performed . TherefoOptimal evaluation of SPT result is particularly important to avoid unnecessary allergen avoidance, dietary restrictions, use of medications, as well as long-term treatment with immunotherapy.The role of physician in allergen SPT:• Be sure that the conditions of the test room are suitable, and educated personnel, equipment and allergen extracts are ready• Consider the patient, patient history and physical examination findings, reconsider deferential diagnosis and test indications, and check whether SPT will provide any additional information, or the results will affect the treatment options• Carefully consider the contraindications for the test and the factors that may influence the test results• Inform the patient about the benefits and the risks of SPT• Choose the allergens in the test panel taking the symptoms and allergen exposure of the patient, and the common allergens in your region into account• Inspect the skin region that will be used for SPT , and prefer forearm• Be sure that the tester has sufficient information on SPT, and can finish the test safely if the test is to be performed by someone else, other than a physician. Stay close to the test room, be ready to treat complications• Analyze the clinical importance of positive test results and false negativity in case of negative allergen responses• Determine the diagnosis and treatment plan• Share the test results and the treatment plan with your patientEducated and experienced nurses and other medical staff may help the physician while performing SPT, and in some other stages of treatment process. The patient should be informed about the test and its possible consequences, and he/she should be comforted before applying the test. An educated and experienced nurse or health technician may apply the test under supervision of the physician, and helps for documentation. The nurse or technician should be educated and ready for a probable complication. He/she should be capable of educating the patients for allergen avoidance and use of an adrenaline autoinjector (EpiPen or Anapen), if the physician needs such a help.SPT is a safe procedure that does not disturb the patient much.On the other hand, some adverse reactions may appear, although rare . Those mThe expected skin reaction in SPT is a localized swelling and itching. The localized skin swelling usually appears as an IgE-related late phase response  . SwellinAllergens may unintendedly pass into the systemic circulation in SPT. Typical symptoms of anaphylaxis including widespread urticaria, angioedema, bronchospasm and hypotension may appear. These systemic reactions are usually mild, and respond to standard treatment. Although rarely reported in large series, a number of papers have reported systemic allergic reactions . In a stA few deaths were reported after IDT, and only one death was reported after SPT (the patient had most of the risk factors listed below) . Late sySystemic reactions occurred particularly in children who had atopic dermatitis and younger than 6 months of age, when tested with food allergens .The risk factors of anaphylaxis in SPT :• Infants and young children (may appear at every age)• Testing with food allergens in the individuals with a previous history of food anaphylaxis• Testing with fresh food and non-commercial allergen extracts• Testing with latex allergen• Presence of asthma (particularly if the disease is active or unstable)• Widespread atopic dermatitis in childrenSince both atopic dermatitis and asthma are frequent disorders and systemic adverse reactions are very rare after SPT, the physician should not be reluctant to perform a SPT on these patients after having sufficient knowledge of these disorders, and taking all necessary precautions.SPT should be performed in a healthcare facility in which a medical team authorized to treat systemic allergic reactions are ready. It is recommended to follow up the patients with positive SPT, the ones with asthma or previous anaphylaxis for at least 20 minutes after completion of SPT (40 minutes after skin pricking) , 196.The minimum standards of emergency equipment and medications , 196:• Oxygen (6 L/min using a mask)• Intravenous fluids for fast infusion in case of hypotension• Adrenaline for intramuscular injection• Salbutamol for use with nebulization or inhalationDetailed information on treatment of systemic allergic reactions and anaphylaxis is out of scope of this chapter.Appendix 6.3.7.5 and Appendix 6.3.7.6.Most of the studies did not give any information whether their patients filled in an informed consent form before SPT. The informed consent form we recommend is given in Keywords: allergic rhinitis, in vivo testing, diagnostic testingIn parallel with the recent technological developments, a number of laboratory test methods have been developed and routinely used for diagnosis of AR. Laboratory tests are widely used in the diagnosis of AR. Generally speaking, laboratory tests used in AR diagnosis intend to identify IgE.In vitro tests have some advantages over in vivo tests in some special circumstances:• In the elderly with cardiovascular disorders, since in vitro tests do not bring any risk for a systemic allergic reaction• In patients who have the risk for a severe anaphylactic reaction• In the patients that cannot stop their medications, since medications do not alter in vitro test results• In infants (<12 months) that cannot produce a satisfactory skin test response • In post-anaphylactic period• In patients with severe and extensive atopic dermatitis or dermographism in whom skin tests may be false positive .IgE is an antibody produced in response to a threat perceived by the immune system. Its level increases gradually in blood after birth, reaches a plateau in the second decade, then declines. Normal IgE level in adults is considered as 100-150 KU/L . Serum IThis is the most frequently used in vitro test in the diagnosis of AR. Allergen specific IgE determination in serum is not influenced by medications, or dermatological disorders. It is employed to screen allergy, and to monitor the effectiveness of immunotherapy. Allergen specific IgE levels in serum and SPT results are well correlated .Specific IgE antibody test aims to detect the level of an allergen-specific IgE in serum. Allergen-specific IgE is produced by a type 1 hypersensitivity reaction in the body.Phadebas radioallergosorbent test  is the first immunoassay test designed to determine allergen-specific IgE in serum. In this method, the patient’s serum is mixed with known allergens to let allergen-specific IgE in the serum bind these allergens, and produce allergen-antibody complexes. The test material is washed to remove excess, unbound IgE. Then, radiolabeled anti-IgE is added, they bind to patient’s IgE that made allergen-antibody complexes with the specific allergen. Measurement of radioactivity gives the amount of allergen-specific IgE in the serum .Nowadays, enzyme-labeled anti-IgE has been used more frequently for immunosorbent analysis (ELISA). The enzymatic reaction produces a colorful product on adding the substrate for the enzyme. Fluorescent enzyme immunoassay (FEIA) and chemiluminescent immunoassay have been developed in parallel with the advances in ELISA technique, and they are now employed to detect allergen-specific IgE in the serum .ImmunoCAP™  and Immulite™  are highly specific FDA-approved methods for quantitative measurement of allergen-specific IgE levels in serum , 202. ThThanks to advances in genetics, pure natural, recombinant allergens  or synthetic peptide panels can be produced for specific IgE tests -207. TheUsually symptom severity is correlated with serum specific IgE levels. It was reported that wheezing and serum specific IgE levels were correlated, however any IgE cutoff level could not be clearly determined for wheezing. The authors concluded that the severity of the symptoms did not only depend on IgE antibodies, but also to the release of mediators and variable responses of the target organ to these mediators (208). On the other hand, serum specific IgE may be undetectable in a patient with allergic symptoms, or may be positive in an asymptomatic individual .Component-based diagnostic testing (CBDT) is a method based on microarray technology, where recombinant allergens are used. In this way, sensitization to allergens can be determined even in asymptomatic patients, using peptide sequences consisting of pure allergen molecules or allergen sequences. CBDT aims to clearly determine the antigenic epitopes to which the patient’s IgE is bound, and to establish a relationship between the IgE measured specific to the subcomponent of allergens and the severity of allergic disease . CBTD isImmunoCAP ISAC  is a commercial example of CBDT. It allows detection of IgE against 112 individual allergens derived from 51 allergen sources .Basophils and mast cells carry high-affinity IgE receptors on their surfaces which activate on exposure to sufficient amount of allergen. Various techniques have been developed to examine basophil responses to allergens. After the discovery of the activation marker CD63 on the basophils by Sainte-Laudy et al. , basophiThese tests aim to determine histamine and leukotriene C4 (LTC4) released from the basophils after treating human blood with allergen. Since live cells are needed to perform the test, the blood sample should be analyzed within 24 hours. These tests are not used in common -220.Some patients have classical AR symptoms in absence of systemic atopy, ie. negative skin tests and serum allergen-specific IgE. This has given rise to the concept of local allergic rhinitis (LAR). LAR is diagnosed in absence of a systemic atopy (negative skin tests and serum specific IgE), and positive nasal allergen-specific IgE or nasal provocation test .Various techniques have been used for detection of nasal allergen-specific IgE including Swab method in which specific IgE is analyzed in 5 ml of isotonic nasal lavage fluid, and ImmunoCAP radioallergosorbent technique  .Keywords: Allergic rhinitis, in vitro tests, nasal cytology, specific IgE, total IgE.Nasal provocation test is based on appearance of symptoms such as nasal edema, congestion and sneezing, and alterations in objective measurements such as decreased nasal airflow following nasal application of an allergen or a non-specific irritant . Nasal pIt should be noted that there should be at least 7 days between provocation sessions. First, saline is administered into the nose as a control solution, then the provocation agent is applied . The mosThe inflammatory cells obtained by scraping inferior turbinate mucosa on anterior rhinoscopy is examined for eosinophils, and if more than 25% of them are eosinophils, this is supportive for AR. The quality of nasal cytology, thus its use in the diagnosis of AR depends on obtaining a satisfactory sample, as well as proper preparation, staining and interpretation by experienced physicians .There are four parameters in this scoring system; namely VAS 1 , VAS 2 , VAS 3 (ocular symptoms) and VAS 4 (asthma symptoms). These parameters provide more accurate diagnosis of AR patients, determine the severity of the disease, and used for making a more effective treatment plan .Chronic airway disorders, nasal infection, sinusitis, otitis media and their co-existence with AR is the main reasons for disturbance of nasal mucociliary clearance . MucocilRhinomanometry is a test that allows us to measure the transnasal pressure changes affecting the airflow through the nose . The preThey are done as psychophysical and electrophysiological tests. Smell sticks are used in psychophysical tests. This test has subtitles such as threshold, discrimination, identification, memory and hedonic scale .Nitric oxide is the primary defense against microorganisms in the upper respiratory tract owing to its antiviral and bacteriostatic activities. It also has an accelerating effect on ciliary motion in the upper respiratory tract . In addiAlong with the technological development, increased expression of RNA (lncRNA) and mRNA which do not encode in CD4 T cells has been detected in AR patients. These are measured using microarray tests .Not indicated in the diagnosis of AR .This is the primary imaging modality in the diagnosis of paranasal sinus disorders . On the Not preferred in the diagnosis of AR. It should be employed in the diagnosis of fungal sinusitis, encephaloceles and tumors , 245.Keywords: Allergic rhinitis, diagnosis, radiologyMethod: A literature search was done on Pubmed, Scopus and Google academic databases with the keywords “non-allergic rhinitis, differential diagnosis”. The meta-analyses were taken into account until 2015. All international studies were reviewed between 2015 and 2018. Older references were reviewed in case of insufficient new data on the topic.Rhinitis is defined as the inflammation of the nasal mucosa. A number of factors may trigger this inflammation including infectious agents, allergy, irritants, medications and hormones. Rhinitis is characterized by presence of one or more of the following symptoms: rhinorrhea, nasal congestion, nasal itching and sneezing . HeadachSome complex pathophysiologic mechanisms give rise to rhinitis symptoms . ChronicIgE does not play a role in the pathophysiology of non-allergic rhinitis (NAR). NAR occurs as a result of nasal hyperactivity against non-immunological stimuli; however, the exact cause of this hyperactivity has not been clearly understood. The blood supply and glandular secretions of the nasal mucosa are under the control of the autonomic nervous system. Stimulation of sympathetic nerves results in release of norepinephrine and neuropeptide Y, causing vasoconstriction of nasal vessels, decreasing mucosal blood flow -252. TheOphthalmic and maxillary branches of the trigeminal nerve are primarily responsible for the sensation of the nose, and nociceptive dysfunction is also thought to play a role in the pathophysiology of NAR , 254. ThChronic rhinitis may be classified into allergic and non-allergic rhinitis. AR is nasal mucosal inflammation triggered by IgE release after exposure to the allergen. The definitive diagnosis is made by allergy tests; either a skin test or an allergen-specific IgE test in serum. In case of similar symptoms and examination findings but a negative allergy test, the patient is diagnosed with NAR. On the other hand, AR and NAR may coexist. Studies on patients with chronic rhinitis showed that 43% of them had AR alone, 23% had NAR alone, and 34% had mixed  rhinitis . These rSometimes it may be difficult to distinguish AR from other types of rhinitis since the diagnostic criteria of different rhinitis types may overlap. The definitive diagnosis is very important since some treatment options that are effective in AR are less effective in other types of rhinitis. On the other hand, it should be kept in mind that NAR may progress to AR over time, and patients with NAR should be re-evaluated at intervals in terms of allergies , 257.It is of great importance to distinguish other diseases that can cause rhinitis-like symptoms from rhinitis; these include anatomical abnormalities such as nasal septum deviation, systemic diseases such as hypothyroidism and diabetes, granulomatous diseases such as Wegener’s granulomatosis, as well as tumors, foreign bodies, cerebrospinal fluid rhinorrhea and nasal polyposis . These dAR is a symptomatic nasal disease triggered by IgE-mediated inflammation following allergen exposure. Allergic patients have a genetic tendency to produce an inflammatory response to materials that are normally harmless to the body. These reactions may also be called as “hypersensitivity reactions” since inflammation developing against such non-pathogenic substances (such as pollen) is unnecessary . The symNAR is diagnosed with the help of negative allergy tests in presence of symptoms similar to AR. It is often difficult to distinguish NAR from AR since both may exhibit similar clinical pictures. The patient has nasal congestion, rhinorrhea, sneezing and / or postnasal drainage, however skin test and / or allergen specific IgE in serum are negative. NAR covers a number of different conditions that cause similar nasal symptoms, therefore it a disease spectrum rather than a single disease.NAR may be classified into eight groups  253, 25, 259. MiThe most frequently encountered NAR type is ‘non-allergic rhinopathy’, previously called as ‘vasomotor rhinitis’ or ‘idiopathic rhinitis’. Although it was believed that inflammation triggered by intrinsic nasal vascularization and abnormalities in the nasal glands played role in the pathogenesis of vasomotor rhinitis, it has recently been shown that neurosensory mechanisms play an important role in the pathophysiology, therefore it is more appropriate to call it ‘rhinopathy’ rather than ‘rhinitis’. Since this group of patients do not have allergy by definition, this disorder is more accurately called as ‘non-allergic rhinopathy’ , 259.Non-allergic rhinopathy may occur episodically or perennially; the triggering factors are environmental factors that usually do not cause any symptoms in normal individuals. These factors include strong odors, temperature, humidity and pressure changes, exposure to cold air, alcohol consumption and hormonal changes during the menstrual period , 260. ThNon-allergic rhinopathy is a diagnosis of exclusion, and the patient history is of great importance. Absence of inflammatory cells including eosinophils, plasma cells and mast cells on nasal cytology helps diagnosis.Unlike AR, patients are older and do not complain of symptoms triggered by exposure to classical allergens, such as pollen and house dust mites. However, as the patients’ complaints may be affected by changes in temperature and humidity, they may state that there are seasonal changes in their symptoms; and this should not be confused with seasonal AR.In non-allergic rhinopathy, sneezing, nasal itching and ocular complaints are less common than AR. The differential diagnosis includes chronic sinusitis, nasal polyps, non-allergic rhinitis with eosinophilia syndrome, aspirin-exacerbated respiratory disease, infectious rhinitis/rhinosinusitis, anatomical abnormalities, medication-induced rhinitis, cerebrospinal fluid rhinorrhea and pregnancy. Intranasal corticosteroids or intranasal antihistamines are primarily used in treatment .Patients with non-allergic rhinitis with eosinophilic syndrome (NARES) present with AR-like symptoms such as nasal congestion, rhinorrhea and nasal itching; however allergy tests are negative. The diagnosis is based on patient history, physical examination, negative SPT or allergen-specific IgE in serum, and nasal eosinophilia on nasal cytology. The nasal turbinates are usually hypertrophic and pale on nasal examination. The risk of developing aspirin-exacerbated respiratory disease later in life is 50%, and 50% of them have bronchial hyper-reactivity , 262. ThGustatory rhinitis is characterized by watery rhinorrhea, which occurs immediately after the first bite of the meal. This occurs particularly with bitter and spicy foods. Gustatory rhinitis is more frequently seen in the elderly, and the vagus nerve is supposed to play role in its pathogenesis , 263. AnThe term “rhinitis medicamentosa” is mostly used to describe the rebound nasal congestion caused by long-term use of topical alpha adrenergic decongestants / vasoconstrictor agents (such as oxymetazoline and phenylephrine). Use of these agents for 3 consecutive days is safe, however their use more than 5-7 days results in tachphylaxis and rebound nasal congestion. The rebound nasal congestion encourages patient to use the agent more, so that the patient goes into a vicious cycle and becomes addicted to these medications. Although the clear mechanism of the disease has not yet been fully understood, current theories focus on recurrent nasal hypoxia and negative neural feedback, and a reduction in the accompanying alpha-2 receptor response .Medication induced rhinitis may also develop with use of some oral medications, including antihypertensives (such as beta blockers and angiotensin converting enzyme inhibitors), chlorpromazine, antidepressants, and phosphodiesterase-5 inhibitors used in the treatment of benign prostatic hypertrophy , 262. AnThe nasal mucosa of these patients tends to seem more erythematous and tends to bleed on nasal examination. The first step in the treatment is to stop the medication that causes rhinitis.Hormones act directly on the nasal mucosa, causing hyperactivity of the mucous glands and rhinorrhea. Hormonal disorders such as hypothyroidism and acromegaly, and changes in estrogen and progesterone levels may predispose to rhinitis , 262.Pregnancy is another hormonal condition that prepares the ground for rhinitis symptoms. Pregnancy rhinitis starts in pregnancy, lasts 6 weeks or more, has no other underlying cause and regresses after birth. It has been supposed that increased circulating blood volume, ponding in vessels and relaxation in smooth muscles causes this condition , 265.Staphylococcus aureus, Proteus mirabilis, Escherichia coli), and particularly Klebsiella ozaenae may cause atrophic rhinitis. However, these microorganisms are also thought to infect the already damaged nasal mucosa secondarily (Atrophic rhinitis can be primary (idiopathic) or secondary. Primary atrophic rhinitis is characterized by atrophy of the nasal mucosa and secretory glands, and is usually seen in young adults. It is observed more frequently in developing countries and hot climates , 266. Paondarily , 266. Seondarily , 266.In atrophic rhinitis, the functional, ciliated respiratory epithelium of nasal mucosa gradually transforms into non-functional ciliated squamous epithelium This leads to disturbance of mucociliary clearance and neurological regulation. Normal nasal airflow is disturbed, causing the sensation of nasal congestion. Although irrigation, moisturizing, topical or systemic antibiotics and various surgical techniques have been recommended for treatment, the results are not satisfactory , 259.Senile rhinitis is a type of rhinitis that is seen in the elderly, causing persistent watery nasal discharge. Patient’s complaints usually increase while eating and with some environmental factors. It can coexist with other types of rhinitis. Since the elderly individuals frequently use medications, medication induced rhinitis may accompany senile rhinitis, and medications may often be the main cause of the condition. This should be kept in mind in the differential diagnosis , 259.Patients with rhinorrhea should be questioned for craniofacial trauma and previous nasal surgery, and cerebrospinal fluid (CSF) rhinorrhea should be excluded in the differential diagnosis, particularly in case of unilateral rhinorrhea , 267. ItAllergic and non-allergic rhinitis may present with similar clinical pictures. Sometimes it is not possible to distinguish these two disorders, and sometimes both allergic and non-allergic rhinitis coexist in same patient. This may cause difficulties in differential diagnosis. A number of studies have been conducted to show the similarities and differences of these two rhinitis types, and to increase the accuracy of the diagnoses. These two conditions may be differentiated by some features.AR usually begins in childhood, and a family history of atopy  is present; NAR usually occurs later in life, and does not show a familial transition. While NAR is more common in females, no gender predilection is observed in AR , 268.While AR symptoms vary between seasons, this is minimal in NAR. Seasonal changes in NAR symptoms are often due to temperature and humidity changes rather than pollen; this should not be interpreted as seasonal AR , 268. ARAlthough carrying out a detailed physical examination is important, the physical examination findings do not contribute much to differential diagnosis. The nasal mucosa is usually pale, edematous and swollen in AR, however the nasal mucosa may be normal, erythematous or atrophic in NAR, and watery rhinorrhea may be observed. Dark circles under the eyes may be observed in AR  , 268. InKeywords: Non-allergic rhinitis, differential diagnosis.Method: Pubmed, Science Direct, Google academic databases were searched using the keywords “nonallergic rhinitis, differential diagnosis, symptoms, triggers”. The international studies published between 2008 and 2017 were included in the review. Expert committee reports were taken into consideration for the topics with insufficient data.Non-allergic rhinitis (NAR) often appears when the patient comes across with non-allergic triggering factors. Examples of these triggering factors are temperature or humidity changes, nonspecific irritant stimuli such as alcohol, cigarette, smoke, powders, automotive emission fumes, chlorine and odors . It is more common in females, and the elderly population has a higher rate of NAR compared to AR . DiagnosHormonal changes in thyroid dysfunction, adolescence, menstruation, menopause and pregnancy have been associated with NAR. Hormonal changes affect nasal homeostasis with disruption of the normal sympathetic / parasympathetic axis. Irritant-induced rhinitis reflects both the effect of chemical irritants and changes in temperature, humidity and pressure on occupational exposures. Cold air changes nasal homeostasis by increasing the release of triptase and other mast cell activation factors. Vasoconstriction or vasodilation in the nose to maintain constant heat and moisture in the nasal cavity may cause edema, obstruction and rhinorrhea in these patients. Exposure to irritant substances at work or at home may initiate an inflammatory response. The responses related to irritant factors may range from spicy food-induced gustatory rhinitis to inhalation of toluene or other industrial products in occupational rhinitis . Marked NARES is diagnosed with a significant level of eosinophilia in nasal cytology and negative allergy tests. The triggering factor of the disease is unknown. The patients with NARES are supposed to have an underlying chronic nasal inflammation that causes eosinophilia and rhinitis symptoms. Nasal polyposis and aspirin intolerance rates are high in these patients.The systemic disorders that present with rhinitis symptoms should also be considered. Churg-Strauss syndrome, Graves’ disease, systemic lupus erythematosus and Wegener’s granulomatosis may be associated with NAR .History is an important component in making the differential diagnosis. Nasal and palate itching, sneezing, symptoms on exposure to allergen, and seasonal symptoms including ocular ones support an allergic disease. Family history also gives an important clue for presence of allergy . RecurreRhinorrhea may be anterior or posterior, may occur as a postnasal discharge, may be due to allergy or not. AR causes bilateral light-colored nasal secretion. Isolated, unilateral light-colored nasal discharge is not common, and CSF leakage should be excluded in this case. CSF leak most often occurs after sinus surgery or trauma, but may also be spontaneous.Transparent nasal discharge may be associated with allergies. Eosinophils give secretion a yellow color whereas neutrophils give it a green color, and this reminds an infection . Nasal cNasal congestion is usually bilateral in AR, however it may be unilateral in some frequent nasal abnormalities including nasal septum deviation . StructuChoanal atresia and encephalocele should also be considered in the differential diagnosis of nasal obstruction in young patients. Subjective nasal congestion is often observed in atrophic rhinitis , or following aggressive inferior turbinate surgery (empty nose syndrome).A number of medications may cause symptoms of rhinitis. The mechanism of action of medications may be local inflammation, neurogenic action, or idiopathic . NeurogeKeywords: Non-allergic rhinitis, differential diagnosis, symptoms, triggers.The examination starts with inspection; mouth breathing, frequent sniffing, nasal speech and scratching the nose may be observed. On inspection, clues of AR such as a horizontal line on the nasal dorsum, red and watery eyes supporting allergic conjuncivitis, and dark folds / shadows under eyes known as “allergic shiners” may be seen.Wegener’s granulomatosis or chronic cocaine use may result in the saddle nose deformity. Nasal polyps may lead to enlargement of nasal framework. Sarcoidosis may cause a purple color on the nasal tip. Severe telangiectasia suggests hereditary hemorrhagic telangiectasia that manifests with epistaxis. Chronic mouth breathing may result from total or near-total nasal obstruction , 274.Endoscopic examination is the preferred method for nasal examination. However, if an endoscope is not available, anterior rhinoscopy can be performed with a headlamp and nasal speculum. Nasal endoscopy is more specific than anterior rhinoscopy, and alters the diagnosis in more than 50% of patients with nasal complaints . In AR, Nasal septal perforation may result from septum surgery, chronic vasoconstriction , Wegener’s granulomatosis, nose picking, and rarely use of nasal corticosteroids , 274.Although the majority of the patients with rhinitis are diagnosed either with AR or NAR, some other rhinitis types worth considering. Polyps, deviation of nasal septum, or traumatic bone fractures causing mechanical alteration in nasal laminar air flow may lead to rhinitis symptoms. Often, these can be identified on anterior rhinoscopy; however, the abnormalities causing occlusion at posterior or superior parts of the nasal cavity may be overlooked on anterior rhinoscopy, and require an endoscopic examination. More importantly, rhinitis may be related to a neoplasm and may cause mechanical obstruction or alter the dynamics in the nasal cavity. Lymphoma has been reported as the most common neoplastic cause of rhinitis .Although nasal septum deviation is frequent, it rarely causes the main symptoms of rhinitis. It may cause unilateral symptoms and cause difficulty of treatment with nasal sprays. Otorhinolarngological examination should cover throat, postnasal region, palate and ears. All patients with rhinitis should have a chest examination including spirometry and peak flow to determine a possible coexisting asthma .Keywords: Anterior rhinoscopy, nasal endoscopy.An underlying allergy is excluded with a negative SPT and/or negative allergen-specific IgE in serum, and the nasal symptoms are categorized in NAR. Infectious diseases, rhinosinusitis and mechanical /anatomical abnormalities are also excluded , 260.SPT and allergen-specific IgE in serum are usually positive in AR. The diameters of induration and erythema are measured 15-20 minutes after pricking in SPT. If the diameter of the allergen induration is ≥ 3 mm or it equals to that of histamine (histamine ≥ 3 mm), the result is considered as positive for that allergen.A number of method-related factors may affect serum allergen-specific IgE results. In particular, the anti-IgE used in the kit should preferably be a mixture of monoclonal antibodies that are specific to more than one epitope in the Fc fragment .Complete blood count, nasal swab, nasal cytology, blood tests for a possible underlying condition , b2--transferrin in nasal secretion , urinalyKeywords: Laboratory investigations, differential diagnosis, radiology.Nasal inspiratory peak flow: Nasal inspiratory peak flow rate is a fast and inexpensive test, the device is small, portable and practical, it can be used easily even in children. It can be used for objective measurements in nasal provocation tests. The results are correlated with rhinoscopic examination in rhinitis, but there are no symptom scores , autoimmune conditions , cystic fibrosis, tuberculosis and ciliary dyskinesia. Other systemic causes should be considered in patients with symptoms that do not respond maximum medical therapy, or when scarring (pemphigus), intense bleeding and crusting (Wegener’s granulomatosis) or submucosal cobblestone appearance (sarcoidosis) are observed in the nasal mucosa. The findings of granulomatous disorders include persistent inflammation and crusting, ulceration, nasal mass formation or mucosal cobblestone appearance in addition to extranasal findings and systemic symptoms. Autoimmune diseases can cause antigen-antibody interaction in the nose, resulting in mucosal ulceration, dryness, crusting and recurrent infection. In cystic fibrosis, the sinonasal findings vary according to the mutation state. The nasal polyps are evident most frequently in patients with ΔF508 mutation, and are often together with bacterial biofilms of Staphylococcuc aureus or Pseudomonas aeruginosa. Tuberculosis often involves the nasopharynx, and results in nasal inflammation and rhinorrhea. Nasal symptoms occur in primary ciliary dyskinesia due to inability to clear mucus from nose and paranasal sinuses, and the diagnosis is made with the saccharin test : It has recently regarded as a subgroup of rhinitis. The allergic reaction of LAR is limited to the nose. Although the local inflammatory response is similar to AR, there is no systemic involvement. Some patients classified as NAR previously are now considered to have LAR. LAR manifests only in the nose, and is characterized by a local inflammation with eosinophilic infiltration, and nasal IgE production in response to aeroallergens. Skin tests performed with aeroallergens and serum allergen-specific IgE levels are negative. LAR is associated with asthma and conjunctivitis, and often begins in childhood  AR may be statistically related to asthma; (b) AR may aggravate concomitant asthma; and (c) AR may have a causal role in the pathogenesis of asthma.The upper and lower airways share the same anatomical, functional, pathogenic, clinical and immunological features, and share the same lymphoid network, thus they activate similar cells when reacting to airborne allergens. These relationships have been extensively studied, and it has been suggested that allergic respiratory disease is a disease in continuum, occurring simultaneously. Several possible mechanisms have been proposed to explain the link between AR and asthma. Braunstahl has shown that an allergen encountered anywhere in the airway may cause a response throughout the airway . FailureNumerous studies have investigated the association of AR and asthma and their comorbid effects. While the prevalence of asthma is less than 2% in those without AR, its prevalence is 10-40% in those with AR, and it has been reported that 80% of asthma patients may have symptomatic AR . Kou et Although different rates have been reported in studies for the association of AR and asthma, it is clear that they are comorbid conditions. Recent studies have revealed that environmental factors play important roles in the etiology of AR and the comorbidity of allergic diseases. The prevalence of asthma and AR may also change depending on smoking, exposure to cigarette smoke and air pollution as well as the distribution of allergens that vary in accordance with the geographical features, climate and vegetation . The coeBoth AR and asthma are chronic inflammatory diseases of the upper and lower respiratory tracts, and similar inflammatory mechanisms and similar cells and mediators play a role in their pathogenesis. The studies clearly showed that the upper and lower airways share common immunopathological mechanisms, and as a result, the term “single airway” or “combined airways” has been used. This term has been based on the evidence that AR is an independent risk factor for the development of asthma .The respiratory mucosa consists of pseudostratified ciliary columnar epithelium and a supporting lamina propria. The airway epithelium acts as a physical barrier against the external environment, is constantly exposed to pollutants, allergens and microbes, and responds directly by regulating adaptive immune responses . The lowTissue remodeling can occur in any organ in response to inflammation or mechanical injury, in order to restore normal tissue. Airway remodeling is considered as the hallmark of asthmatic lung, and is often associated with more severe phenotypes . Today, AR is mainly driven by Th2 cell-related inflammation. Upper and lower airway samples obtained with bronchoscopy in patients with AR and allergic asthma showed similar Th2 cell-induced inflammation in the nasal and bronchial mucosa . ConsideA study that analyzed the molecular mechanisms underlying a multi-comorbidity of asthma, eczema, and rhinitis identified a series of proteins and cellular processes that are common in these atopic disorders. In this study, it was observed that asthma and rhinitis shared numerous interrelated proteins. The authors reported that there were 15 pathways including IL4 and GATA3-related pathway in the multi-comorbidity of asthma, eczema, and rhinitis, and a number of proteins were obtained potentially related to this multi-comorbidity processes .The presence of AR causes aggravation of asthma attacks, and lengthens hospital stay in asthmatics. It has been shown that treating AR causes a reduction in asthma costs and hospitalization. ARIA Guideline suggest that asthma patients should be evaluated for AR, and AR patients for asthma . Early aAR therapy should be individualized in patients with concomitant asthma. Administration of oral antihistamines and particularly nasal steroids have been shown to reduce bronchial hyper-reactivity and improve asthma control. Lohia et al.  conducteAlthough leukotriene receptor antagonists are not used in the primary care of the patients with AR alone, it may be a viable choice in case of simultaneous AR and asthma . To dateKeywords: Allergic rhinitis, asthma.As defined in the European Position Paper on Rhinosinusitis and Nasal Polyps (EPOS 2020), rhinosinusitis (RS) is inflammation of the nose and the paranasal sinuses characterized by two or more symptoms, one of which should be either nasal blockage/obstruction/congestion or nasal discharge , and/or facial pain/pressure and/or reduction or loss of smell. On endoscopy, nasal polyps (NP) and/or mucopurulent discharge mainly from middle meatus and/or edema/mucosal obstruction are evident. On CT, there are mucosal changes in the ostiomeatal complex and/or sinuses. The definition of acute rhinosinusitis (ARS) in children is similar to aforementioned definition, but there is symptom of “cough” instead of “a decrease or loss in smell”. These findings are defined as ARS if they are present for less than 12 weeks, and as chronic rhinosinusitis (CRS) if they are present for a longer period. CRS, on the other hand, is divided into two groups as “with nasal polyps” and “without nasal polyps” .The association of AR and RS has been the subject of many studies. Although the coexistence of AR and RS has been shown in most of the studies, there is no clear definition whether they are risk factors for each other. The results of the studies are also contradictory. Although some studies report that patients with sinusitis have a higher prevalence of AR with a positive prick test compared to the general population, others contradict this finding. Most of the discussions on this issue are due to the fact that most of the studies are old, and that there were no definitions of CRS and AR at that time. The patients included in the study were not classified as ARS, CRS with polyps or CRS without polyps, as stated in EPOS. On the other hand, susceptibility to CRS may differ with regard to the type of AR, since it has been reported that patients with perennial AR were more susceptible to CRS compared to the ones with seasonal AR .The connection between AR and RS may be explained by various mechanisms. One of these is the blockage of the ostiomeatal complex due to mucosal edema caused by inflammation induced by IgE-mediated mechanism of AR, prevention of mucociliary transport of the sinuses, and development of bacterial colonization thereon. Another mechanism is significant eosinophilic inflammation, particularly in the maxillary sinus, in allergic patients during the allergen season. When the ethmoid and nasal polyp tissues of patients with CRS are examined, local T cell infiltration, mediators such as IL-4 and IL-5, and Th2-type cytokine profile dominance were observed in the ethmoid mucosa and nasal polyps of the patients with CRS. These cytokines stimulate local IgE production, cause regional eosinophil infiltration, and prolong eosinophil life. Nasal allergen provocation or natural allergen exposure causes eosinophil migration into the paranasal sinuses .The prevalence studies showing the coexistence of AR and RS reported different rates. İbanez et al.  includedInflammation in AR may disturb mucociliary motility, and make the patient prone to ARS. The results of the prevalence studies on simultaneous appearance of AR and ARS are quite diverse. In 1992, Furukawa concluded that allergy was an important factor in sinusitis based on the analysis of AR and ARS studies and a number of summaries (307). Mbarek et al. , studiedMelvin et al.  investigIn the light of all these contradictory findings, one may say that although AR is not considered as a definite risk factor for ARS, it is beneficial to keep AR in mind, to perform tests for the diagnosis of AR in case of clinical necessity, and to add AR treatment in case of sinusitis, particularly in pediatric patients with recurrent ARS findings.Studies on CRS w/o NP showed TNF-alpha, IL-4, IL-5 and IL-8 as mediators. The etiopathogenesis of CRS w/o NP is multifactorial. There are no controlled studies showing the relation of CRS w/o NP with AR. Prevalence studies reported AR prevalence in CRS patients in a wide range, varying between 36.2% and 84%. The patient populations are heterogeneous in most of the studies. The patients with and without NP, and even patients with fungal sinusitis were included in the same study. The reason for widely varying prevalences is the lack of clear distinctions, as stated in EPOS. There are only 3 cross-sectional studies that compared allergic and non-allergic patients with a group of patients with CRS w/o NP, carrying the current diagnostic symptoms for at least 12 weeks. Kirtsreesakul and Ruttanaphol divided the patients that were symptomatic for at least 3 months into two groups by performing a prick test, and compared their plain sinus radiographs and nasal endoscopic examinations. Although they did not find a significant difference between the two groups for endoscopic findings, they detected 2.8 times more abnormalities in the allergic patients compared to non-allergic ones . In 1999In a study by Sedaghat et al.  in 2013,DeYoung et al.  conducteThe presence of AR (as determined by a positive RAST or skin test) in CRS patients does not affect the severity of the disease, degree of involvement of sinuses on CT scan, or the possibility of surgical failure when compared to non-allergic CRS patients. Therefore, the effect of AR on CRS is variable, but small. However, patients with CRS should be questioned about the symptoms of AR, and allergy should be tested in case of clinical suspicion. Regarding treatment, it is recommended that anti-allergic therapy be added to the treatment of patients with chronic sinus disease and associated allergies .Similar to AR, Th2 pathway is active in CRP w/ NP, and the disease is characterized by high IL-5, IL-13 and IgE levels, and eosinophilic inflammation. Local mucosal IgE production and an increase in serum IgE levels are frequently observed in patients with NP. It has been suggested that when sensitive patients are constantly exposed to inhaled allergens, the polyclonal IgE antibodies contribute to persistent inflammation in CRS w/ NP. Pathophysiologically, allergy and CRS w/ NP overlap . HoweverTan et al.  performeDespite conflicting reports in the literature, the prevalence of allergy is higher in patients with CRS w/ NP compared to the general population and patients with CRS w/o NP. Th2 type inflammation, eosinophilia and increased IgE constitute the major underlying pathophysiology, which resembles to AR pathophysiology. However, clinical evidence supporting the relationship between CRS w/ NP and AR is quite weak.Keywords: Allergic rhinitis, sinusitis, rhinitis.Allergic conjunctivitis is a hypersensitivity reaction affecting the eyelids, conjunctiva and / or cornea, causing itching, stinging, redness, edema and watering in the eye , 330. AtSimultaneous AR and allergic conjunctivitis is called as allergic rhinoconjunctivitis (329). AR and conjunctivitis usually coexist. This situation was explained by nasoconjunctival reflex and a pathophysiological type 1 reaction in the nose and eye. Allergic conjunctivitis is the typical conjunctival reaction that occurs after allergen exposure. It affects 15-20% of the population. More than 75% of rhinitis cases with pollen allergy also have conjunctival symptoms . PatientVernal keratoconjunctivitis usually affects children and young adults. It is most frequently observed in temperate and subtropic regions, but may be seen all over the world. Although approximately 50% of the cases have AR, asthma, and atopic dermatitis, any relationship with atopy has not been shown . In addiAtopic keratoconjunctivitis is associated with eczematous lesions of the eyelids and skin. There is dermatitis on the eyelids, face and trunk. Mild to severe chemosis may be seen. There may be giant papillae and conjunctival scarring, and Tarantas spots can be seen, similar to vernal keratoconjunctivitis. Atopic cataract may also develop .Giant papillary conjunctivitis is not a true allergic disorder; irritation is the main etiologic factor. It is characterized by giant, medium or small papillae in the upper palpebral conjunctiva. Conjunctival appearance resembles vernal keratoconjunctivitis . HoweverKeywords: Allergic rhinitis, allergic conjunctivitis.Inflammation is the main incident in comorbid diseases associated with AR. AR may coexist with acute sinusitis, acute otitis media, serous otitis media and adenoid hypertrophy .Otitis media is the inflammation of the middle ear cavity. It is the most common disease in childhood following viral upper respiratory infections. Acute otitis media is an infection in which acute signs of infection such as fever and pain occur. On the other hand, otitis media with effusion (OME) is a non-infectious inflammation usually accompanied by Eustachian tube dysfunction, without acute signs of infection, defined by the accumulation of serous fluid in the middle ear. It often causes hearing loss in children.The correlation of EOM with allergic disorders is still controversial. It has been reported that 24-89% of the children with OME had AR . The mosExamination of the middle ear fluids of AR patients and non-atopic controls collected while inserting tympanostomy tubes revealed significantly higher numbers of eosinophils, T lymphocytes and IL-4 and IL-5 positive cells in children with AR who had at least one allergen positivity in the skin test. T2 cytokines were also shown in torus tubarius and adenoid samples of atopic children with OME. However, IFN-gamma-positive cells were prominent in non-atopic patients with OME -342.In case of positive history and AR symptoms, it is recommended to administer anti-allergy treatment in patients with OME and AR . AllergyKeywords: Allergic rhinitis, otitis media with effusion.Gastroesophageal reflux (GER) is a chronic disorder characterized by the reflux of stomach contents into the esophagus. Patients with AR frequently complain of chest pain and GER . GER mayEosinophilic esophagitis should be considered in differential diagnosis in patients with resistant GER symptoms. Studies support that GER and eosinophilic esophagitis may be different clinical presentations of the same disease .The coexistence of allergic disorders such as eczema, asthma and AR, and the importance of an allergic background have been emphasized in patients with GER and eosinophilic esophagitis. Eosinophils are thought to migrate to the esophagus in response to digested and inhaled allergens in eosinophilic esophagitis , 348. ThLaryngopharyngeal reflux (LPR) should be investigated in patients with cough and hoarseness.Gastrointestinal symptoms of classical reflux may not be seen in LPR. Endoscopic findings of reflux esophagitis are not evident in 50% of the patients, and the severity of esophagitis and LPR may not be equivalent since the upper airway epithelium is more sensitive to the effects of gastric acid than the esophageal epithelium. Patients may experience postnasal discharge, chronic cough, irritation and need for cleansing the throat, as well as other findings such as chronic sinusitis and otitis . It was Post-infectious, allergic and nonspecific factors cause chronic upper airway inflammation in patients with chronic rhinosinusitis findings including chronic cough, rhinorrhea and nasal obstruction. AR is the most common cause in patients with symptoms of chronic rhinosinusitis, such as cough, sneezing, nasal congestion and discharge. GER should be kept in mind in the differential diagnosis particularly in cases that do not respond anti-allergic treatment, and antireflux therapy should be added to AR treatment.Keywords: Allergic rhinitis, gastroesophageal reflux, laryngopharyngeal reflux.Nasal congestion, mouth breathing and snoring are frequent both in patients with adenoid hypertrophy (AH) and AR. AR and AH symptoms overlap particularly in childhood. The relationship between AR and AH has not been yet clearly revealed despite numerous investigations. Since epidemiological studies have been conducted on patients in different age groups, their results are contradictory. The volume of adenoid tissue increases with age starting from birth, and reaches a maximum between the ages of 5-6 years. Then, its size gradually decreases until the age of 8-9, and adenoids are rarely seen in the adults. The larger series on the relation of allergy and AH have been conducted by Evcimik et al. . AH was In the light of aforementioned findings, one may consider that AR may be important for AH in some age groups, or AH may coexist with AR. However, it is not clear whether AR causes AH, or that AH triggers AR symptoms. Doğru et al. found AH in 118 (21.2%) children among 566 children with AR, and stated that persistent AR was more common in children with AH. Among AR patients, they detected moderate rhinitis in 90 (76.3%) patients with AH, in 274 (62.6%) of those without AH, and reported that AH increased the severity and extended the duration of the disease . Ameli eThe size of adenoid may affect the severity of symptoms in children with AR. Nuhoğlu et al.  comparedSome investigators analyzed immune mediators in the adenoid tissue. They hypothesized that AH might develop due to immune responses in the adenoids. They showed that CD1a + Langerhans cells, eosinophils and IL-4 and IL-5 mRNA positive cells were more in number in the adenoid tissues of allergic children compared to non-atopic ones -363. AlaSome authors claimed that anti-allergic treatment might be beneficial, and be an alternative to surgery in patients with AH. Although there is no sufficient data for antihistamines, a number of studies reported the benefit of nasal corticosteroids. Chohan et al.  includedAlthough the exact role of AR in the etiology of AH has not been demonstrated, allergy should be questioned in all children with symptomatic AH, and anti-allergic treatment should be administered in case of a positive history. Adenoid examination should be done particularly in preschool children with AR. On the other hand, double-blind controlled studies are needed to clarify the relationship between AH and AR, and the role of medical therapy in this relationship.Keywords: Allergic rhinitis, adenoid hypertrophy.Cough affects about 10-20% of adults, and it has three main etiological factors: upper airway cough syndrome , asthma, and gastroesophageal reflux (GER). Cough may frequently be seen in AR and sinusitis. In these diseases, postnasal secretions stimulate nerve endings in the hypopharynx and larynx. Sensitivity to environmental factors is another cause of cough. Cough becomes more severe when both environmental and endogenous factors come into play. Aspiration of postnasal discharge and nasal secretions may result in cough, and its severity may increase due to underlying disorders such as asthma, cough-variant asthma, eosinophilic bronchitis and GER .Chronic upper respiratory cough syndrome  and / or subclinical inflammatory changes in the lower respiratory tract have been mainly blamed for the stimulation of the afferent nerve endings in patients with AR. Some studies reported increased reactivity at these nerve endings. Cough responses to capsaicin were compared in the patients with pollen allergy in the pollen season and out of the pollen season. The responses of allergic and non-allergic patients were also compared out of the pollen season. Cough responses to capsaicin was better in the pollen season in patients with pollen allergy. The allergic patients had better cough response to capsaicin compared to non-allergic patients in out of pollen season -370.Keywords: Allergic rhinitis, cough.Staphylococcus aureus colonization are seen in both conditions  filters reduce house dust mites . Nasal sThe use of acaricides may improve AR symptoms , 396. MaPresence of high moisture and molds in the house increases the risk of AR and rhinoconjunctivitis . There iThe most efficient and sustainable allergen avoidance may be achieved by educating hypersensitive individuals on measures for indoor allergens, and changing their habits .Pollen is the first allergens identified by Charles Blackeley in 1860. In order for pollens to cause an allergic reaction, they should be present in the environment in high concentrations, transported by wind, and have antigenic properties. Pollens are small male reproductive units with a diameter of 5-200 microns, containing a large number of cells. Pollen contains a large number of allergic proteins. These proteins cause symptoms in hypersensitive individuals. The pollens small enough to be carried by the wind are significant in terms of allergy. They can be transported to very long distances and enter indoors .The size of the pollen is important for the symptoms. Big pollens are allergens of upper airway and conjunctiva while small ones may reach to lower airways and cause symptoms.The most frequent allergens causing AR show regional differences. The climate and vegetation are different in all geographical regions of Turkey. Types and numbers of pollens show differences in terms of regional temperature and climate. The pollen concentration in the atmosphere varies depending on the regional vegetation, the amount of precipitation, and the direction and speed of the wind. The pollen calendar is the first step for allergen avoidance. Now, pollen collectors are placed in the city centers, and the pollen calendars are available in almost every country, including ours .The highest amounts of pollens in Turkey originate from Cupressaceae , Pinus (pine), and Gramineae (grass), and the pollens are in the air between March and June .The main pollens causing allergy are meadow grass, weed and tree pollens. Tree pollination takes place between February and May, grass pollination occurs in June and July, and weed pollination continues from August to the last months of the year. In addition, some pollens are in the air between March and November. The diameter of pollens usually range between 5-100 microns .People who are allergic to pollens are mostly symptomatic when the weather is dry, hot and windy. The pollen amount in the air is the highest in the morning hours. If possible, the patients should not spend time outdoors or wear a mask during these hours. The bedroom window should not be opened in the morning, and the windows should be closed when going to bed at night in the pollen season. There should be air conditioners with a pollen filter in the house and cars, the car window must be kept close in the morning. Recirculation mode should be turned on in the air conditioner of the car .The patient should take a shower as soon as he/she returns home, or wash his/her face with plenty of water. Sprays may be used for nasal cleaning. Outfits such as coats and vests worn outside should be shaken outside while entering the house, and should not be kept in the bedroom . PollensThe bedroom should be protected from pollens as much as possible, and remain as a safe area. Outerwear should be changed as soon as entering the interiors. Although recommended, it is not always possible to change the place of residence for those who have extensive complaints due to the pollens.In case of being in the park, garden and green areas at the weekends, the nose and face should be washed with plenty of water, and a nasal douche must be performed.Mold spores are responsible for both perennial and seasonal allergies. Their size is 2-250 microns. Outdoor molds peak in mid-summer, and their number decrease when the weather gets cold . The numToday, especially in Europe, there are centers and mobile applications that track the pollens in the air and make the pollen maps to inform patients . Pollen Keywords: Administration oral, administration intranasal, allergic rhinitis, anti-allergic agents, beclomethasone dipropionate, betamethasone, budesonide, ciclesonide, corticosteroids, dexamethasone, flunisolide, fluticasone furoate, fluticasone propionate, methyl prednisolone, mometasone furoate, nasal sprays, prednisolone, safety, triamcinolone acetonide.Systemic corticosteroids have never been proposed as the first line treatment options in AR Guideline , 96. HowThe short-acting corticosteroids may be administered through oral route. On the other hand, long-acting corticosteroids may be used parenterally, as depot injections. Oral prednisolone may be started at a dose of 20-40 mg/day . Then, tSide effects of systemic steroids include infections, adrenocortical insufficiency, diabetes, peptic ulcer, glaucoma, and moon face development. Systemic corticosteroids should not be preferred in the presence of diabetes mellitus, severe hypertension, severe peptic ulcer, severe osteoporosis, glaucoma, herpetic keratitis, psychotic disorders, tuberculosis and similar chronic infections , 412.Systemic corticosteroids may be used for their systemic anti-inflammatory effects for ophthalmic, nasal and general complaints of allergy. In addition, they may be used in patients refractory to other treatment options, particularly the ones with hyposmia. Short-term systemic corticosteroids may be administered to those who have severe perennial rhinitis, AR accompanying nasal polyps and in case of permanent risk for anosmia . More ofNasal corticosteroids (NCS) are effective in treatment of AR , 96, 415It has been shown that NCS are effective on all symptoms of moderate /severe AR, including sneezing, itching, nasal congestion, rhinorrhea and ocular symptoms , 96. TheAll NCS are similar for their efficacy. The onset of action is usually 2-8 hours after application, however the maximum effect is evident 7-14 days later . RegularRhinosinusitis, nasal polyposis, smell disorders, adenoid hypertrophy, lymphoid hyperplasia in the nasopharynx, obstructive sleep apnea, Eustachian tube dysfunction, otitis media with effusion, atopic dermatitis, asthma, allergic conjunctivitis, chronic cough, laryngitis, and accompanying gastroesophageal reflux are the main comorbid conditions of AR , 430. ApHypertrophic adenoids may get smaller and the volume of the nasal cavity may increase with the use of NCS , 433-435NCS are tolerated well. Crusting, dryness, epistaxis, and burning sensation are rare local adverse effects. Patients may complain of bitter taste and a bad smell , 427. ItRecent studies compared mometasone furoate and fluticasone furoate since they are the most widely used nasal preparations . Some auThe prevalence of epistaxis has been reported in a wide range. There are rare reports in the literature concerning nasal septal perforation due to long-term use of NCS . No signIn order to analyze the effects of NCS on the hypothalamic-pituitary-adrenal axis, 2-4 weeks of kinemometry was performed for their short-term effects, and 12 months of stadiometry was employed for their long-term effects , 446. AlNumerous different corticosteroids have been administered intranasally from past to present. A first generation corticosteroid, dexamethasone, is no longer preferred due to its side effects . The secBeclometasone dipropionate is a prodrug. Others become less active quickly, and produce fewer side effects with minimal systemic absorption. Water-soluble agents such as budesonide pass into the systemic circulation in higher amounts unlike lipophilic fluticasone and mometasone . The lipLaser aerosol spectrometry was used to study the droplet sizes and distributions in the nasal cavity after use of NCS sprays. Droplet storage was detected in a larger mucosal area with fluticasone furoate containing nasal preparations compared to the ones containing fluticasone propionate and mometasone furoate . TriamciDifferent molecules used in nasal preparations are comparable in efficacy and treatment compliance. NCS are usually prescribed at a dose of two puffs into each nostril, once or twice a day . RecentlThe American Academy of Otolaryngology and Head and Neck Surgery (AAO-HNS) has prepared AR diagnosis and treatment Guideline. They have strongly recommended use of NCS in patients with AR, particularly when the disease affects quality of life  2016 revIn conclusion, NCS are well tolerated by the patients, and may be the first treatment option in patients with moderate/severe intermittent and mild persistent AR, as well as in patients with moderate/severe persistent AR.Keywords: Histamine, H1 antihistamines, anti-allergic medications, medications, anti-allergic agents, antihistamines, allergic rhinitis, antagonistsTraditionally, oral antihistamines are the first-line treatment options for AR patients worldwide. First generation H1 antihistamines are lipophilic. In addition to crossing the blood brain barrier and binding to histamine receptors, they block muscarinic, adrenergic (or adreno-ceptors) and dopaminergic receptors, causing sedation and cardiovascular, urinary and gastrointestinal adverse effects , 494. NeAR is actually a systemic disease. Allergic symptoms begin 6-12 hours after exposure to the allergen, and peak at 12-24 hours. Apart from nasal symptoms, oral antihistamines are effective in ocular itching, irritation and redness, oral and pharyngeal symptoms, and all dermatological symptoms , 493. ToSecond generation antihistamines are the most preferred treatment agents for the treatment of allergic symptoms thanks to their high selectivity for the H1 receptors, as well as their high efficacy and less side effects . On the In addition to sedation, use of first-generation antihistamines may result in traffic accidents. Diphenhydramine is a well-known molecule in this regard. Aviation accidents were examined, and it was reported that the most commonly used medication in deceased pilots was diphenhydramine. Local airline pilots are approved to use second-generation antihistamines  in the USA . In anotThe most frequently prescribed second generation antihistamines are cetirizine, desloratadine, ebastine, fexofenadine, levocetirizine, loratadine, bilastine and rupatadine. The antihistamines curently in use are listed in Cetirizine is a second-generation antihistamine with a proven efficacy in patients with perennial AR at a dose of 10 mg/day. Although it showed a significant improvement in symptom severity compared to placebo, adverse effects such as headache and performance impairment were also observed . LearninLevocetirizine has been shown as the best treatment option when compared to other second-generation antihistamines due to its beneficial effect on persistent AR , 501. VaAlthough cardiac side effects of second generation antihistamines are extremely rare, a high risk of ventricular arrhythmia was reported with ebastine , and itsBilastine is a non-sedative oral antihistamine with proven in vitro and in vivo selectivity for the H1-receptors. It is not metabolized by cytochrome P450 system . Ninety-Rupatadine was launched in 2003 as an antihistamine with a strong H1 receptor blocking activity and anti-PAF effect. It has a wider mechanism of action, used in the treatment of chronic urticaria and AR , 507. RuThe second generation antihistamines registered in Turkey, and their trade names are presented on Adverse effects of H1 antihistamines are due to their binding to receptors other than H1 . First gResearch has shown that adverse effects of bilastine were minimal when compared to placebo. Studies on healthy volunteers confirmed that it had minimal effects on psychomotor performance, even when administered up to four times of the recommended dose . StudiesThere are several case reports on hepatic toxicity due to levocetirizine and its active R-enantiomer . Cases wInternational allergy study groups including ARIA and International Primary Care Respiratory Group (IPCRG) emphasized that second generation antihistamines should be used as a first-line treatment in patients with AR, and new generation drugs should be preferred. Therefore, non-sedative antihistamines constitute the backbone of allergy treatment. In addition, symptoms and concomitant diseases as well as severity of the symptoms are important for the selection of the therapeutic agent. Therefore, the authors of this chapter prefer a patient-specific treatment approach and medication selection. Easy tolerability, a good safety profile and price are important factors for drug selection, but it is considered that all second-generation antihistamines have acceptable sedative properties, and do not impair learning.The second generation antihistamines in Turkey are comparable for their effectiveness to control AR symptoms, therefore the selection of drug depends on its adverse effect profile, particularly CNS suppression. Possible sedative effects, wide therapeutic index, appropriate pharmacokinetics and low-dose administration should be considered for selection of an antihistamine. The profession of the patient is of particular importance for antihistamine selection since even a small sedative effect may have serious consequences in some professions.Antihistamines have been used for more than seventy years in the treatment of allergic disorders. Although the topical treatment approach has been used extensively in the respiratory tract for centuries, oral route has been preferred for antihistamine treatment in AR. The advantage of topical administration is less systemic absorption and hence smaller risk for systemic adverse effects. Nasal administration of antihistamines has been popularized in the past two decades .Nasal antihistamines also have anti-inflammatory activities in addition to their antihistamine activity . Their aAlthough nasal antihistamines exert their anti-inflammatory effects at their daily recommended doses, oral antihistamines need to be used at much higher doses than their recommended dose to show their anti-inflammatory effects. Therefore, recent Guideline have reported that nasal antihistamines may be used as first-line therapy in AR .Today, there are two approved nasal antihistamines: azelastine and olopatadine , 529.Azelastine is a phthalazinone derivative, a second-generation antihistamine with a high affinity for H1 receptors. Its affinity for binding to H1 receptors is ten times higher than chlorpheniramine . NasallyThe most common side effects expressed by patients using azelastine are bitter taste, headache, drowsiness and nasal burning sensation .Olopatadine selectively blocks H1 receptors, and it also inhibits the release of histamine and other pro-inflammatory mediators from the mast cells . RandomiThe most frequently expressed side effects are bitter taste, headache, epistaxis, and pharyngeal pain. The prevalence of drowsiness was found in less than 1% of the patients .In multicenter placebo-controlled studies comparing the efficacies of olopatadine and azelastine, no significant difference was found between these two agents concerning efficacy. Both agents were well tolerated with low adverse effect profiles. Bitter taste sensation was less with olopatadine .Oral antihistamines have been preferred in treatment of AR despite their side effects such as dizziness, sedation and limited effectiveness in terms of nasal congestion .A number of recent controlled studies reported that azelastine had fewer side effects, and had similar efficacy or superior than loratadine, desloratadine, fexofenadine and cetirizine , 541-544There are no studies in the literature comparing olopatadine with oral antihistamines.In a meta-analysis of nine studies comparing azelastine with NCS, it was found that NCS provided a more effective improvement in the nasal symptoms of AR although no difference was reported for ocular symptoms . Three mA study comparing olopatadine and fluticasone reported that there was no clinically significant difference between the two groups in terms of mean two-week symptom reduction, however it was concluded that olopatadine was more effective in the first 3 days of treatment, and its therapeutic effect appeared in a shorter time .Comparison of azelastin, mometasone and placebo revealed that the effect of azelastine started in the first 15 to 45 minutes after the application, and the superiority of azelastine continued for the first 8 hours after this application. In the comparison of azelastin with fluticasone spray and oral cetirizine tablet, it was found that the effectiveness of azelastine started within the first 30 minutes, and it was superior to all other agents in the first 24 hours .A study comparing olopatadine and mometasone determined that the effectiveness of olopatadine started in the first 30 minutes and continued for 12 hours. It was observed that mometasone and placebo produced the same effect in the first 150 minutes .In the light of the aforementioned studies, it has been concluded that intranasal antihistamines have a more rapid onset of action compared to all other medications used in allergy treatment.Patients using azelastine nasal spray, fluticasone nasal spray, and azelastine-fluticasone combination were analyzed for clinical improvement after two weeks, and the improvement rates were reported as 5%, 27% and 37.9% in the groups of azelastine, fluticasone and combination groups, respectively . In studThe combination of NCS and intranasal antihistamines may be a good choice in the treatment of AR due to advantage of topical application and additive effects of the molecules .In conclusion;Nasal antihistamines are good treatment options in AR treatment due to the advantage of direct application to the nasal mucosa. Both azelastine and olopatadine show a fast onset of action, minutes after nasal administration. Both agents’ efficacies are similar with or superior to oral antihistamines, and they have been found to have superior efficacy for nasal congestion. Nasal antihistamines have similar efficacy with NCS. Combinations of a nasal antihistamine with NCS will be a good option in the treatment of AR due to their local application advantage and additive effects of the molecules. Another advantage of nasal administration is direct delivery of the drug to the target tissue, in a higher concentration, thereby minimizing the side effects seen in systemic administration. The most frequently reported side effects are bitter taste and sleepiness. Nasal antihistamines have been recommended in the recent Guideline as the first-line treatment options due to their efficacy and safety.Keywords Perennial allergic rhinitis, Seasonal allergic rhinitis, Montelukast, Leukotriene antagonistsLeukotrienes (LT) are inflammatory mediators released from leukocytes. They play role both in the early and late phases of the allergic response . CystenyAdministration of antileukotrienes are divided into two groups in relation with their mechanism of action:1. Cystenyl leukotriene receptor antagonists (LTRA) block LT receptors, thus the final organ response. This group includes montelukast, zafirlukast and pranlukast.2. Leukotriene synthesis inhibitors (5-lipoxygenase inhibitors) block the synthesis of cystenyl LTs and LTB4. Zileuton, ZD-2138, Bay X 1005 and MK-0591 are in this group .Montelukast is the only cystenyl LTRA approved for AR in Turkey. It is indicated for the treatment of asthma and AR. Montelukast has FDA approval for seasonal AR treatment in adults, and children 2 years and older. It has also been approved for treatment of perennial AR in adults and children 6 months and older . Its useMontelukast is effective on four cardinal symptoms of AR including nasal congestion, rhinorrhea, itching and sneezing. In addition, it is also beneficial on sleep disturbance due to nasal congestion . Lately,Montelukast improves both rhinitis and asthma symptoms in patients with simultaneous seasonal AR and asthma . LTRAs eRecent publications reported that combination of montelukast and fluticasone propionate improved symptoms and quality of life scores in patients with moderate-to-severe AR better than fluticasone and placebo . A descrErdoğan et al.  performeIn the 2010 revision of the ARIA report, it was stated that LTRAs were effective in seasonal AR in children and adults, and in perennial AR in preschool children. However, it was recommended that oral H1 antihistamines should be preferred over oral LTRAs since they were less costly . ARIA 20In seasonal AR, it has been recommended to prefer NCS over LTRAs because they are more effective. There are no systematic reviews comparing the efficacies of NCS and LTRAs in perennial AR .LTRAs may be more useful than oral antihistamines in patients with AR and asthma, and particularly in exercise-induced asthma and aspirin-exacerbated respiratory disease . InhaledMontelukast is usually well-tolerated and does not cause sedation. Its most frequent side effect in children is abdominal pain (0.23%) . AlthougKeywords: Allergic rhinitis, anti-allergic agents, Histamine H1 antagonists, corticosteroids, antihistamines, nasal decongestants, nasal sprays, administration oral, administration intranasal, mometasone furoate, desloratadine, montelukast, montelukast sodium, azelastine, loratadine, cetirizine, pheniramine, cromolyn sodium, chlorpheniramine, cholorpheniramine maleate, fluticasone, fluticasone propionate, leukotriene antagonists, azatadine maleat pseudoephedrine sulfate drug combination, carbinoxamine, carbinoxamine maleate, dexbrompheniramine maleate, phenylephrine hydrochloride, pheniramine maleate.Combined preparations registered in Turkey and other countries :1. Desloratadine + montelukast sodium2. Desloratadine + pseudoephedrine HCL3. Desloratadine + pseudoephedrine sulfate4. Pseudoephedrine HCL + cetirizine HCL5. Pseudoephedrine HCL + triprolidine HCL6. Pseudoephedrine HCL + acrivastine7. Pseudoephedrine HCL + chlorpheniramine maleate8. Pseudoephedrine sulfate + loratadine9. Pseudoephedrine sulfate + dexbrompheniramine maleate10. Pseudoephedrine sulfate + azatadine maleate11. Levocetirizine dihydrochloride + montelukast sodium12. Azelastine HCL + fluticasone propionate13. Cromolyn sodium + phenylpropanolamine14. Carbinoxamine + phenylephrine15. Carbinoxamine maleate + phenylephrine HCL16. Phenylephrine HCL+ chlorobutanol + chlorpheniramine17. Phenylpropanolamine HCL + pheniramine maleateKeywords: Allergic rhinitis, anti-allergic agents, histamine H1 antagonists, antihistamines, administration oral, desloratadine, montelukast, montelukast sodium, azelastine, loratadine, cetirizine, pheniramine, chlorpheniramine, cholorpheniramine maleat, leukotriene antagonists, carbinoxamine, carbinoxamine maleate, dexbrompheniramine maleate, pheniramine maleateOral antihistamine + leukotriene receptor antagonist combinations are more effective than oral antihistamines alone on rhinorrhea, nasal itching, ocular symptoms, sneezing and daytime symptoms. However, further studies are needed for night symptoms, nasal congestion, ocular symptoms and quality of life .Montelukast is not the first treatment option in AR treatment due to its weak efficacy compared to both oral antihistamines and NCS. However, when combined with oral antihistamines, it provides significant superiority in nasal symptom scores compared to placebo, and shows treatment efficacy equivalent to NCS. Therefore, it is recommended to be combined with oral antihistamines .From the pharmacological point of view, and compared to use of montelukast alone, it has been shown that the standard preparation, in which desloratadine is combined with the usual montelukast dose, has no effect on the bioavailability of montelukast, and can be used safely . CombiniAnother combination of oral antihistamine and leukotriene receptor antagonist, montelukast + fexofenadine, has been shown to reduce total nasal symptom scores more than the combination of montelukast + levocetirizine, and is a more cost effective option .Oral antihistamines are effective on sneezing, itching, rhinorrhea and ocular symptoms, while LTRAs are less effective on all nasal and ocular symptoms. On the other hand, both medications are not quite effective on nasal congestion, and therefore the use of combination products is advantageous in some respects .Combination of desloratadine + montelukast improved sleep-related symptom scores more than desloratadine alone in patients with AR, therefore desloratadine + montelukast combination is superior to desloratadine alone, particularly for night symptoms .Keywords: Allergic rhinitis, anti-allergic agents, histamine H1 antagonists, administration oral, desloratadine, azelastine, loratadine, cetirizine, pheniramine, chlorpheniramine, chlorpheniramine maleate, azatadine maleate pseudoephedrine sulfate drug combination, carbinoxamine, carbinoxamine maleate, dexbrompheniramine maleate, phenylephirine hydrochloride, pheniramine maleateThe combination of cetirizine and pseudoephedrine (cetirizine 10 mg + pseudoephedrine 120 mg) is superior to cetirizine and pseudoephedrine alone in terms of nasal congestion in the first two hours of pollen exposure, and it is more effective than the use of both agents individually in AR treatment .A review including four studies on the combination of desloratadine and pseudoephedrine has reported that the combination was more effective than desloratadine or pseudoephedrine alone in terms of decongestion at the beginning (the second day) of AR treatment, and may be considered in the treatment of AR patients when nasal congestion was the main symptom .A multicenter, randomized, controlled, double-blind study reported that desloratadine + pseudoephedrine combination has more antihistamine and more decongestant activity compared to individual use of these active ingredients, and it was superior to individual use of these two agents not only in nasal congestion, but in all nasal and non-nasal symptoms of seasonal AR. The authors also stated that the adverse effects of this combination was not more than the side effect of the decongestant alone. Therefore, they recommended combined use of desloratadine and pseudoephedrine rather than their individual use in seasonal AR treatment .Keywords: Allergic rhinitis, anti-allergic agents, histamine H1 antagonists, administration oral, desloratadine, azelastine, loratadine, cetirizine, pheniramine, chlorpheniramine, cholorpheniramine maleate, carbinoxamine, carbinoxamine maleate, dexbrompheniramine maleate, pheniramine maleate, mometasone furoate, desloratadine, azelastine, loratadine, cetirizine, pheniramine, chlorpheniramine, cholorpheniramine maleate, fluticasone, fluticasone propionateA randomized controlled clinical trial comparing the combination of oral desloratadine + prednisolone with dexchlorpheniramine maleate-betamethasone in childhood AR concluded that both combinations provided effective treatment, but the desloratadine + prednisolone combination offered fewer side effects and easier dosing .Keywords: Allergic rhinitis, anti-allergic agents, histamine H1 antagonists, corticosteroids, antihistamines, nasal sprays, administration intranasal, mometasone furoate, desloratadine, azelastine, loratadine, cetirizine, pheniramine, chlorpheniramine, cholorpheniramine maleate, fluticasone, fluticasone propionate, azatadine maleate pseudoephedrine sulfate drug combination, carbinoxamine, carbinoxamine maleate, dexbrompheniramine maleate, pheniramine maleateThe combination of NCS with nasal antihistamines provides significant improvement in total nasal symptom scores compared to use of NCS and nasal antihistamines alone . The comThe use of azelastine + fluticasone combination provides an additional benefit in moderate/severe  and persAzelastine + fluticasone combination provides efficacy equivalent to sublingual immunotherapy  and otheKeywords: Allergic rhinitis, anti-allergic agents, histamine H1 antagonists, corticosteroids, nasal decongestants, nasal sprays, administration intranasal, mometasone furoate, fluticasone, fluticasone propionate, phenylephirine hydrochlorideThe combination of nasal mometasone furoate and oxymetazoline is more effective than nasal mometasone furoate alone in the first 1-4 hours of treatment in terms of decongestion and superior to nasal oxymetazoline alone for the continuance of decongestion. It is recommended in seasonal AR particularly for ensuring rapid onset of treatment .Keywords: Perennial allergic rhinitis, Seasonal allergic rhinitis, Omalizumab, Anti-IgEOmalizumab is a subcutaneously administered recombinant human monoclonal anti-IgE antibody. It reduces the level of free IgE and prevents binding of IgE to high affinity IgE receptors by binding to the Fc portion of the free-circulating IgE antibodies, hence, it blocks allergic inflammatory reactions. It also reduces the expression of high affinity IgE receptors (FCeRI) on basophils and mast cells. It also reduces the numbers of eosinophils, lymphocytes and other inflammatory cells in the respiratory tissue .There is a meta-analysis on the use of omalizumab in AR. It reported that omalizumab significantly reduced symptom scores and need for use of other agents, and improved quality of life in patients with moderate-severe AR, whose symptoms could not be controlled with conventional treatment . In addiCurrent data indicate that omalizumab is considered as a new treatment agent in moderate-severe AR patients who have allergen-specific antibodies and do not respond to conventional pharmacotherapy. In addition, omalizumab may be useful in patients with simultaneous AR and asthma . HoweverOmalizumab is usually well-tolerated except for its few serious adverse effects. Local reactions at the injection site, side effects such as viral infections, sinusitis, headache, pharyngitis and rarely urticaria, anaphylaxis and anaphylactoid reactions, thrombocytopenia and alopecia have been reported. In controlled studies on malignancy potential, no difference was found between groups receiving and not receiving omalizumab therapy . Cases wThe ARIA group recommends omalizumab in patients with AR and asthma with an obvious IgE-dependent allergic component, and in asthma patients who cannot be treated despite optimal pharmacological therapy and appropriate allergen avoidance. They do not have any recommendations regarding the use of anti-IgE in patients with AR not accompanied by asthma .Keywords: Allergic rhinitis, Perennial allergic rhinitis, Seasonal allergic rhinitis, Cromolyn sodiumCromolyns are mast cell stabilizers that act in acute phase reaction by preventing mast cell degranulation and histamine release . They alThe reports on the effects of cromolyns include an evidence-based report and a meta-analysis , 601. ExThe current literature emphasized that use of intranasal 4% sodium cromoglycate spray 4 times/day for 4 weeks improved symptom scores in patients with mild-to-moderate AR, and reduced nasal neutrophilic aggregation and PAF release in nasal secretions . In a raNasal cromolyns are safe agents, and they can be used safely in children and pregnant women. Nasal cromolyn may be considered as the first-line treatment for AR-related rhinorrhea, sneezing and itching symptoms in pregnant women . It can According to ARIA criteria, nasal cromolyns are recommended for AR treatment owing to their excellent safety profiles, however nasal antihistamines are recommended over cromolyns since they are more effective, and have a higher patient compliance. Ocular cromolyns may be administered in mild conjunctivitis seen with AR in children or adults, due to their good safety profiles. However, the need to apply 4 times a day may result in a poor patient compliance .Keywords: Allergic rhinitis, decongestant, systemic, topicalSympathomimetic amines  and imidazoline derivatives  used as decongestants bind a- adrenergic receptors, and lead to norepinephrine release and hence vasoconstriction and decreased mucosal edema directly  or indirectly (pseudoephedrine). Sympathomimetic amines usually bind to α-1 receptors, while imidazoline derivatives bind more selectively to α-2 receptors. However, both groups include decongestants (pseudoephedrine and oxymetazoline) that can bind non-selectively to α-1 and α-2 receptors .Oral decongestants exert a sympathomimetic effect by stimulating a-adrenergic receptors and increasing adrenergic activity. In this way, they cause vasoconstriction in the upper respiratory tract, paranasal sinuses and nasal mucosa, and decrease the volume and mucus secretion of edematous mucosal tissues , 607.Regulation of mucosal vascular network and particularly filling and emptying cycles of the cavernous venous plexus are important in the regulation of air flow in the nasal cavity and the feeling of congestion. Venous plexuses are surrounded by adrenergic nerve endings, which offer binding to α- and β-adrenergic receptors, similar to the arterioles accompanying them. β receptors have vasodilator and a receptors have vasoconstrictor capabilities. Pseudoephedrine and phenylephrine which act on α-adrenergic receptors in the nasal mucosa, eliminate nasal congestion by exhibiting vasoconstrictive effects in the nasal vascular structures .Pseudoephedrine and phenylephrine are the most frequently used systemic decongestants due to their sympathomimetic effects. Pseudoephedrine increases noradrenaline release, and has an indirect agonistic effect on peripheral α-1 and cardiac β-adrenergic receptors. Phenylephrine is more selective for α-1 receptors, and has a weaker agonistic effect on α-2 and β receptors. Phenylephrine exerts most of its agonistic effect on α-adrenergic receptors directly, and a small amount of indirect agonistic effect is achieved with a slight increase in noradrenaline release .Phenylproponolamine, on the other hand, is not preferred today due to its serious systemic side effects (risk of cardiovascular adverse effects and hemorrhagic stroke in women) , 611.Prolonged-release tablets may extend the action of oral decongestants on nasal congestion up to 24 hours. Oral decongestants may be used alone or in combination with oral antihistamines .In a randomized placebo-controlled study on patients with AR, the effect of single-dose pseudoephedrine on reducing nasal congestion was significantly higher in the 6-hour observation period compared to placebo and phenylephrine. It was also reported in this study that there was no significant difference between phenylephrine and placebo groups . AnotherIn conclusion, the results of few studies indicated that nasal congestion could be reduced with pseudoephedrine, while phenylephrine was ineffective in patients with AR .The use of systemic decongestants is restricted due to their systemic side effects (psychotropic and cardiovascular effects). Their main known side effects are insomnia, irritability, anorexia, anxiety, tremor, tachycardia and increased blood pressure. Because of these side effects and the concern for their acceptability, it is recommended that oral decongestants should be used short-term in patients with AR, and should not be used in the elderly and in certain patients  , 597. AnAlthough it has been shown that the oral decongestants are effective in reducing nasal congestion in children over 6 years of age, prolonged-release formulations at a dose of 120 mg is not recommended in children under 12 years of age. Children under the age of four are more susceptible to toxicity, and the safe dose range has not been defined. In children under two years of age, the central nervous system stimulator effect can lead to psychosis, ataxia and hallucinations. Therefore, systemic decongestants should be administered to the patients under 6 years of age only after assessing the risks and benefits of therapy , 608.Nasal decongestants lead to vasoconstriction owing to their α-adrenergic stimulating effect on vascular smooth muscles, they also decrease inflammation. Although they improve nasal congestion in patients with AR, they do not have any effect on other symptoms of AR. It has been known that the effect of nasal administration is superior to systemic administration for improving nasal obstruction. Short-term use of nasal decongestants may be recommended particularly in presence of persistent nasal obstruction in patients with AR , 616.Nasal administration of xylometazoline and oxymetazoline provides temporary but rapid elimination of nasal obstruction owing to their strong vasoconstrictive effects. However, long-term topical use results in an increase in symptomatic nasal congestion (rhinitis medicamentosa). The pathophysiology underlying rhinitis medicamentosa is not clearly known, however it is believed that the amount of endogenous norepinephrine in the presynaptic interval decreases with negative feedback due to long-term use of a nasal decongestant. When decongestant is stopped, it is supposed that sympathetic activity decreases due to insufficient norepinephrine, parasympathetic activity becomes dominant, and as a result, “rebound congestion” occurs as a further increase in nasal secretion and vasodilation. In addition, as long-term use of topical decongestants will cause desensitization in α receptors, the patient will need to increase the dose of medication to achieve the same effect .The duration of decongestant use leading to the development of rhinitis medicamentosa is controversial. While some studies have shown that prolonged use up to 8 weeks does not cause rebound nasal congestion, other studies have shown that even 3-day use may result in rhinitis medicamentosa. Largely, it has been accepted that the risk of rhinitis medicamentosa increases significantly when a decongestant is used more than 10 days. The recommended period of administration is less than 3 days , 617.Known side effects of nasal decongestants are nasal burning and tingling sensation, mucosal ulcerations, epistaxis and dryness. Although nasal decongestants have a strong decongestant effect, these side effects may occur due to the rebound nasal congestion and their negative effects on mucociliary activity ,597.Some studies showed that the side effects of nasal decongestants (oxymetazoline) such as tachyphylaxis and rebound congestion were reversible when they were combined with NCS. They also claimed that combined nasal decongestant and NCS preparations were more effective than use of NCS alone in the relief of nasal symptoms .The use of decongestants during pregnancy, particularly in the first trimester, may lead to anomalies such as gastroschisis, endocardial cushion defect, ear anomalies and pyloric stenosis. Therefore, their use is not recommended during pregnancy .The use of decongestants is not recommended in the elderly due to their adverse effects on cardiovascular, urinary, central nervous and endocrine systems. They should not be used particularly in those with a history of glaucoma or disorders of cardiovascular, urinary tract, and vascular systems , 618.According to the ARIA Guideline updated in 2016, the American Academy of Otolaryngology – Head and Neck Surgery (AAO-HNS) Guideline, and the International Consensus Report published in 2018, use of systemic pseudoephedrine is a “recommendation”, and the use of phenylephrine is a “counter-recommendation”. The use of intranasal decongestants is reported as “optional / preferential” , 417.Keywords: Allergic rhinitis, Perennial allergic rhinitis, Seasonal allergic rhinitis, Ipratropium.Anticholinergic agents decrease the parasympathetic stimulation by preventing acetylcholine binding to muscarinic receptors. Nasal anticholinergics prevent secretion of the nasal mucous glands, and provide a reduction in aqueous rhinorrhea. The only nasal spray preparation with anticholinergics contain ipratropium bromide, which is effective in controlling rhinorrhea in both AR and non-allergic rhinitis . The nasThere are no meta-analyses in the literature on the use of ipratropium bromide in AR. ARIA 2010 revision recommended use of nasal ipratropium bromide for rhinorrhea in perennial AR patients . It was Nasal ipratropium bromide has a fast onset of action, and it is recommended to use it three times a day for maximum effect. It is not effective on nasal congestion, sneezing or itching. Its local side effects include dry nose, irritation, burning, epistaxis, dry mouth, and headache, however systemic anticholinergic adverse effects are rare. On the other hand, it should be used with caution in patients with benign prostatic hypertrophy and narrow-angle glaucoma due to risk of systemic adverse effects .Keywords: Immunotherapy, mechanism of action, history, indication, contraindication.Allergen specific immunotherapy (SIT) is a long-term therapy aiming to reduce symptoms that develop due to allergic AR, allergic conjunctivitis, allergic asthma and insect stings, and it results in permanent relief of symptoms by allergen desensitization after the end of the treatment .Allergens are proteins or glycoproteins that can bind to IgE. Most allergens are natural substances present in the nature, such as pollens, animal hair, molds, insects and food. Immunotherapy regulates the immune system to increase host defense against microorganisms. SIT is a treatment method that alters the IgE-mediated immune response by long-term administration of the allergen extract in subclinical and increasing doses, and it aims to improve the symptoms appearing on exposure to that allergen. SIT aims to increase the quality of life of the patient and prevents the progression of the allergic disease in the long term by providing clinical and immunological tolerance . Yılmaz Noon used SIT first in 1911 to vaccinate himself for the pollens that he defined as “aerogenic toxins”. The first randomized controlled study on SIT was performed by Frankland and Agustin in 1954. The serious and even fatal side effects of subcutaneous immunotherapy (SCIT) have led researchers to seek a safer way. Sublingual immunotherapy (SLIT) was developed as a new alternative to SCIT, and was accepted as an alternative method to SCIT in 1998 by the World Health Organization .The patients should provide an informed consent form for SIT due to medicolegal issues. Immunotherapy should be interrupted in the pollen season in patients with seasonal AR. SIT should be discontinued immediately if anaphylaxis develops during treatment . The indA late phase allergic reaction consisting of eosinophils, basophils, mast cells, T cells and macrophage infiltration occurs 6-12 hours after exposure to the allergen. The inflammatory process continues with the release of inflammatory cytokines and mediators from these cells . SIT redThe patient compliance is the most important problem in the selection of patients for SIT.As shown in the recent systematic reviews, the nasal and ocular symptoms improved, and the need for medication decreased with SIT -634.Current Guideline on AR and asthma have reported that SIT is particularly indicated for the treatment of moderate to severe intermittent or persistent AR symptoms, which respond poorly to pharmacotherapy. The allergen extracts for SIT include pollens of grasses, trees and weeds; house dust mites, molds and animal skins. However, given the effectiveness and reliability of SIT directly depends on the quality of the extracts, the use of standardized extracts is an important point in clinical practice , 635.There are different methods for the treatment of allergic asthma and AR / conjunctivitis. In fact, each of the three main treatment methods, namely SIT, avoidance of allergen and pharmacotherapy, have their own benefits, risks, and costs. The severity, duration, and need for medical treatment of symptoms should be taken into account. In addition, the treatment must be tailored individually for each patient, considering his/her preferences. The severity of the disease and the response to previous treatments are also important in this planning .In addition, appearance of the side effects of pharmacotherapy is an indication for SIT, as well as the patients who want to reduce or discontinue long-term treatment .Treatment is recommended to be started early, as the effectiveness of SIT against asthma is higher in children and young adults. Moreover, unlike pharmacotherapy, in which treatment is continued uninterruptedly in order to have a symptomatic well-being, the fact that the clinical benefit continues for 3-5 years after SIT is terminated makes this treatment more advantageous in young patients -638. AppThe initial dose of immunotherapy, target maintenance dose and immunotherapy schedule should be determined by the physician. SIT treatment may be divided into two phases, as the initial phase and the maintenance phase. In the initial phase of treatment, increasing amounts of allergen extract are given in the first 8-28 weeks of treatment. In traditional SIT calendars, one dose increase is made for each visit, and the frequency of the visits varies 1-3 per week.SIT injections can cause local and systemic reactions. Severe reactions often develop within 30 minutes after injection. In addition, systemic reactions associated with immunotherapy may occur later than 30 minutes. Patients should be informed about early and late systemic reactions and how to proceed when they develop before beginning SIT.Local reactions can be managed with local treatments such as cold application or topical corticosteroids, or with systemic antihistamines. Systemic reactions can be moderate or severe. Epinephrine is the first treatment option in patients with anaphylaxis. Antihistamines or systemic corticosteroids are the secondary medications for controlling systemic reactions, and they can never replace epinephrine in the treatment of anaphylaxis. In severe cases, intravenous fluids and oxygen supplementation may be necessary. The immunotherapy dose, schedule, and risks / benefits of continuing treatment should be reassessed in cases who had systemic reactions.Different tests and bioparameters are used to evaluate the clinical efficacy of SIT. Two criteria are taken into consideration when analyzing the clinical results, namely the scoring done by the patient and the scoring done by the physician , 640.There are primary and secondary outcome parameters to evaluate the clinical outcomes of SIT treatment. The severity of symptoms and the need for simultaneous medical treatment are the primary outcome parameters. Specific and general quality of life scores and cost effectiveness are the secondary outcome parameters. A number of additional evaluation methods including cytokine analysis, and cell activation or proliferation markers have been used to comprehend the immunological mechanism of SIT or to demonstrate its therapeutic efficacy.The World Allergy Organization (WAO) stated that both symptom scoring and scoring for the need of medical treatment should be done .Each symptom should be specified daily on a 4-point scale: 0: No symptoms, 1: Mild symptoms  2: Moderate symptoms  3: Severe . This scoring method has been approved by authorized institutions in the USA (FDA) and Europe (EMA).Although there are different opinions in the literature regarding the duration of treatment, it is usually accepted that the treatment should be continued for at least 3-5 years. However, further extension of this period provides a longer symptomatic control -644. DesConsidering the known side effects of SIT, allergens have been developed to produce an immune response without triggering the pathways that cause allergic symptoms or classical side effects of SIT. Peptide immunotherapy uses soluble synthetic peptides that are recognized by T cells, and unlike conventional allergen extracts, they are standardized. Peptide immunotherapy has shown promising results in the treatment of cat, bee venom, house dust mite and grass pollen allergy. Peptide immunotherapy performed for 3 months with synthetic peptide T cell epitopes of cat allergen reduced the symptoms of rhinoconjunctivitis in 2 years following the termination of treatment , 646.Recombinant allergens are commercially produced purified proteins, and they have high safety and efficacy. These genetically modified or natural phenotype allergens reduce IgE-related side effects of SIT, and can provide long-term immunity .Immunostimulant adjuvants are therapeutic agents that aim to increase the immunogenic properties of certain specific allergens without pharmacologically activating them. They have been used in vaccines for many years, however the idea of using them in SIT was introduced later.In genetic vaccines, plasmid DNA or mRNAs that carry the genetic information of the allergen is used instead of the allergen itself. The genetic material is taken up by local host cells located in the dermis, and converted into protein in vivo. These allergenic proteins produce a T1-mediated antigen-specific CD4 and CD8 T cell response. Toll-like receptor-mediated innate immune response is generated by the genetic material itself .Allergens are coated with recyclable nanoparticles. They allow allergen release in vivo in a delayed-continuous or pulsatile form. They can modulate the immune response with fewer side effects. It was demonstrated that recombinant birch pollen coated with PLGA (polylactic-co-glycolic acid) nanoparticles regulated the ongoing T2 cell response after a single dose , 650.Keywords: Allergen immunotherapy, treatment effectiveness, treatment outcome, treatment, withholding, treatment cessationThe widely accepted approach in immunotherapy is subcutaneous injection.SCIT is regarded as the gold standard in studies. SCIT is recommended for patients who have positive skin tests and do not get sufficient benefit despite maximal medical therapy, or cannot tolerate pharmacotherapy as well as for patients with AR and asthma, who do not want to use pharmacotherapy for a long time .The effective treatment dose or maintenance dose is the maximum tolerable dose not causing severe local or systemic side effects. SIT is continued in the form of regular injections for 3-5 years after reaching the maximum tolerable maintenance dose. The dosage schedule differs according to conventional, cluster, rapid protocols and the allergens .After starting treatment in conventional SCIT, the maximum concentration is reached with weekly injections, then the maintenance dose is administered at 4-8 week intervals. The maintenance dose may be achieved with 8 injections in 3 days .Every company in Europe has its own standards. The standard is determined by the reactivity in the skin test. The maximum tolerable maintenance dose is determined based on the major allergen content of the vaccine .In conventional immunotherapy, subcutaneous injections in weekly increasing doses reaches to a maximum level in 3-4 months (50000-100000 SQ-U / ml), then injections are done monthly. Vaccines should be stored in the refrigerator; as high temperatures may reduce the activity of the allergen. They must be transported in a cold chain .It is necessary to make sure that the names and doses of the allergen extracts contained in the bottles are clearly and correctly labeled. The label on each bottle should contain the name, surname, date of birth and identification number of the patient.SIT is indicated for AR, asthma, and venom, pollen, house dust mite, and cat-dog allergies .Dermatophagoides pteronyssinus, Dermatophagoides farinae), bee venom, cat, dog and mold allergen extracts are used in SCIT. The extracts may contain only one allergen, or multiple allergens. However, attention should be paid to the interaction of allergens with each other. Some allergens may reduce the effect of others , house dust mites , depot , allergoid, polymerized, with glycerin or lyophilized. The preparation method of extracts affects the efficacy and reliability of SCIT. Side effects are less in treatment with standardized allergen extracts .Allergoid extracts are created by modifying allergens with gluteraldehyde or formaldehyde, and allow administration of high allergen doses. Allergovit  is used in a scientific research project by Mısırlıgil et al.  in 2012.Vaccines should be stored between +2 and +8 degrees, on the door of the refrigerator . In the Key words: Rhinitis, allergic, subcutaneous, injection, immunotherapy.The maintenance dose is the dose injected at the maximum concentration that the patient can tolerate. Maintenance doses used by different companies are shown in In SCIT’s cluster scheme, weekly or biweekly injections are performed.The scheme is not changed for delays up to 7 days. For delays 8- 13 days, the previous dose is repeated.For delays 14 -21 days, the previous dose is reduced by 25%.For delays 21-28 days, the previous dose is reduced by 50%. Then, the dose increase is continued according to the previous scheme at each visit until the ideal dose is reached.th, 14th and 21st days after the maintenance dose is reached. This dose scheme was not based either on retrostpecitve or prospective studies, and a patient-based approach may be an option to be followed , cluster, rush or ultrarush protocols may be employed for subcutaneous immunotherapy. It takes 4-6 months (1-2 injections per week) in the classical protocol, 1 month  in cluster protocol, days in rush protocol and 3-4 hours in the ultrarush protocol to reach the maintainance dose.Maintenance dose schedule varies in different protocols and studies. Low dose is ineffective, and it is not recommended as it may increase the hypersensitivity of the patient .Dose adjustment should be made when switching to a new concentration and bottle, or if patients with a high sensitivity are symptomatic during the pollen season, or if a reaction develops after injection. In these cases, the injections are interrupted .Keleş et al.  studied Polosa et al.  used a sIn classical subcutaneous immunotherapy, the allergen is injected in increasing concentrations over 8-16 weeks and is continued for 3-5 years, which is the conventional duration for immunotherapy. Since SIT requires frequent and regular injections and the injections are recommended to be performed in a hospital, it is troublesome for the patients. The scientific research project by Mısırlıgil et al. has shown that the use of allergoids  allows a reduction in the frequency of injections, and does not require a maintenance dose schedule. In this study, the meadow pollen allergoid and placebo groups were compared. Treatment started with pre-seasonal injections and the maintenance dose was reached in 7 weeks, the induction phase was shorter, dose increase was done in accordance with the individual tolerance of the patient, and maintenance doses were not administered .Side effects related to injections are classified into local and systemic reactions. Indurations larger than 5 cm are considered as a local reaction. Systemic reactions are divided into 4 grades .Common skin lesions are seen in grade 1, including redness, itching and urticaria. In grade 2, in addition to the grade 1 reactions, the mucosa is affected; rhinoconjunctivitis, itching in mouth and angioedema are seen. In grade 3, mild or moderate asthma occurs in addition to the symptoms in grade 2. In grade 4, severe urticaria and asthma, hypotension, weakness, dizziness, abdominal pain, nausea and vomiting are observed. When classified in relation with the occurrence time of the reaction, the reaction is called as an “early reaction” if it occurs within the first 30 minutes after injection, and as a “late reaction” if it occurs later than 30 minutes. There is also a difference in relation with the protocols applied.Side effects may vary depending on the type of allergen extract, injection schedule, allergen preparation and dosage .The patients must be questioned for use of beta blockers or ACE inhibitors, history of asthma attacks before SCIT injections, and their lung capacity should be evaluated with a respiratory function test before starting treatment. Accompanying uncontrolled asthma or cardiovascular diseases  are contraindications for SCIT. Therefore, every patient should be evaluated in terms of asthma before SCIT. The use of beta blockers or ACE inhibitors poses a risk to patients. SCIT is contraindicated in patients who had severe systemic reactions .Given that the vast majority of systemic reactions develop within the first 30 minutes following injection, patients should be observed for at least 30 minutes .Injections should be performed by trained personnel, after the necessary equipment is provided, due to the risk of systemic reactions and anaphylaxis. Side effects should be well monitored, and physical examination results and vital signs should be recorded regularly.In the international evaluation report, a death related to SCIT injection has been reported. The mortality rate was calculated as 1-2 in approximately 2.5 million SCIT injections. The presence of uncontrolled and symptomatic asthma and the presence of a big positive skin reaction on prick test have been blamed for the appearance of systemic reactions. Increasing the dose in the pollen season also increases the risk for systemic reactions. Controlling asthma symptoms before injection largely reduces deaths .Polysensitized patients are at higher risk than monosensitized ones. Systemic reactions mostly occur within the first 30 minutes after injection. However, polysensitized asthmatic patients are more likely to have late reactions. Therefore, these patients should be monitored for more than 30 minutes, for at least 1 hour .Local and systemic side effects may be seen after SCIT. According to the Ring and Messmer classification, side effects are divided into four grades. Due to the risk of fatal side effects, SCIT has been recommended to be applied and followed up by experts in centers with emergency intervention opportunities. Incorrect dose adjustment, accompanying signs of uncontrolled asthma, and use of beta blockers and ACE inhibitors increases the frequency of systemic reactions. Therefore, the current medications of the patient should be questioned before the injection, asthma findings should be examined, and respiratory functions should be evaluated with PEF or FEV1 .The most common side effects are local reactions. Studies have shown that small-sized local reactions are asymptomatic, and do not interfere with continuing treatment. It has been emphasized that the dose should not be increased when a local reaction sizing 2.5-3 cm occurs, and the dose should be reduced when a 3-5 cm or larger local reaction is seen.In light of this information, it is concluded that SCIT can be used safely in both adults and children.Key words: Immunotherapy, allergic rhinitis, elderly, child, systemic reaction, safety.SIT is effective in improving symptoms, reduces the use of medications for symptom control, and is the only intervention that can change the course of the allergic process . SIT hasSIT has been practiced for over a hundred years. However, upon coming across with the serious side effects and even death, safer administration routes have been sought in SIT, including oral, nasal, bronchial, lymphatic and sublingual routes. SLIT was proposed as an alternative to SCIT in the 1980s, and significant progress has been achieved over the past 30 years . The firSLIT comprises ingestion of allergen-containing extracts after keeping the drop or tablet form under the tongue for a few minutes. In the initial phase, allergens are administered at certain intervals in a solution, at doses that are too small to produce an allergic response. The dose of allergen is gradually increased until switching to the maintenance dose, once a week for several months in SCIT. The maintenance phase is reached when the highest and most effective dose is reached; this is the dose that the patient can tolerate, and does not cause any systemic reactions. The treatment period is minimum 3, and maximum 5 years. In SLIT, while the allergen is applied initially every day, it is applied 3 days a week after passing into the maintenance phase. SCIT requires monthly doctor visits, but not daily dosing. In SLIT, the patient can administer treatment at home after the initial dose. SLIT is generally considered to have a better safety profile than SCIT. The main difference between the two routes of administration is that the dose in SLIT contains at least 50-100 times more allergens compared to SCIT, because low doses are generally ineffective in SLIT to achieve a similar level of efficacy with SCIT -674. TheConstant exposure of the oral mucosa to microorganisms or foreign bodies does not result in any infection or inflammation, and this was the starting point of SLIT administration -677. HanWith continued treatment, there is a decrease in mast cell sensitivity, decreased IgE secretion from mucosal B cells, and an increase in antigen-specific IgG. Sublingual Langerhans cells transform allergen-specific Th2 cells into Th1 cells, increase lymphocyte tolerance to the allergen, thereby creating immunomodulation .SLIT may be a treatment option in serum IgE positive, prick test positive patients with a clinical response to the allergen, the patients with moderate or severe symptoms, the patients with symptoms that cannot be controlled with pharmacotherapy, the patients who cannot receive medical treatment due to their side effects, the patients who do not want SCIT, and the patients who do not want to use medical treatment for a long time.SLIT is contraindicated in patients with serious cardiovascular or immunological disorders, in the presence of uncontrolled asthma, malignancies, beta-blocker use, during pregnancy (for beginning the treatment), chronic oral mucous diseases and acute infection , 682. ImSublingual immunotherapy applications consist of initiation (dose increase) (10 IR / mg) and maintenance phases (300 IR / mg).SLIT commercially is available in drop or tablet forms. There are ready-to-use starter and maintenance sets in their special boxes. In the initial treatment set, there are 3 or 4 allergen extracts with increasing concentrations in each bottle. These are called bottles 1, 2, 3 and 4, respectively. In some products, the starter set starts with number 0. Each numbered bottle is a 1:10 diluted version of the next bottle (eg. number 1 is 1:10 diluted form of number 2). The application starts as 1 drop from the bottle 1, containing the smallest concentration of allergens in the treatment set. The patient should drip the drop under the tongue, wait a few minutes, and then swallow it. Treatment is continued by increasing 1 drop each day, and 28 drops are reached on the 28th day. The next day, treatment is continued from the bottle no. 2, at a dose of 1 drop. Again, 28 drops are reached by increasing the number of drops each day. This is repeated for bottles 3 and 4. The patient reaches the maximum dose at the end of the starter set, and this is the maintenance dose .The maintenance treatment set contains the bottle with the highest concentration, bottle 3 or 4, used in the initial treatment. After reaching the maximum dose, the dose is not increased in the maintenance phase, it is kept the same, and is applied 3 days a week.Treatment should be planned for at least 3 years. The success of the treatment depends on well-informing the patient, a good follow up, and the patient’s compliance. The patient should be scheduled for regular follow-ups. Although there may be individual differences, the symptoms usually disappear completely at the end of the treatment, while there may be little response or even no benefit from the treatment in some patients. It may take 6 months to 1 year to have a clinical response. SLIT should be stopped if there is no reduction in symptoms at the end of the first year. Investigations have shown that 3-5 years of immunotherapy provides long-term efficacy in patients with AR. Immunotherapy has been shown to be protective for the development of asthma in the future in patients with AR.Side effects often occur at the beginning of treatment. Local side effects occur in the oral mucosa, and they constitute the majority of side effects (75%). Itching or swelling, sore throat, and burning in the throat may be seen. Systemic reactions include gastrointestinal symptoms such as nausea, abdominal pain, diarrhea, rhinoconjunctivitis, very rarely generalized urticaria, and anaphylaxis. No deaths have been reported due to SLIT -687. SomKey words: Allergic rhinitis, allergic rhinitis treatment, sublingual immunotherapy, immunotherapy.One of the important developments in AR treatment in recent years is the introduction of oral SLIT tablets. These tablets, which are used daily, contain allergens that dissolve rapidly under the tongue.Two SLIT tablet brands have been approved for grass allergy in our country, Europe and USA. These are meadow grass (timothy grass) SLIT tablet , and 5 grass pollen SLIT tablets . Other SLIT tablets, namely ragweed SLIT tablet  and house dust mite SLIT tablets  still has no approval for use in our country.Five grass pollen SLIT tablets are available in two forms: 150 and 300 IR. Adults use 300 IR tablets once a day, for the specified period  Table 7.For meadow and ragwort SLIT tablets, it is recommended to start treatment at least 12 weeks before the beginning of the pollen season. This period is 4 months for five grass pollen SLIT tablets. House dust mite SLIT tablets can be started at any time of the year. If pollen SLIT tablets are started during the pollen season, the patient should be informed that symptoms may increase and medical treatment may not be sufficient for symptom control .Disease modification effects of SLIT tablets were investigated in two long-term studies. In the first of them, a significant improvement was observed in the AR symptom scores after 3 years of use of the meadow grass SLIT tablet, and in 2 years after the cessation of therapy. With this study, meadow grass SLIT tablet was approved for long-term use in America and Europe . SimilarThe most common side effect of grass pollen SLIT tablets are mild to moderate oral reactions . These reactions usually appear with the first dose, and regress within 14 days and do not require treatment. Similar side effects have been observed with other SLIT tablets . Mild gaKeywords: Immunotherapy, sublingual immunotherapy, tablets, side effects, dosage.PATIENT’S NAME - SURNAME:GENDER:DATE OF BIRTH:REGISTRATION NOID NUMBERDear Sir or Madam,This written form has been prepared to explain the basic information about allergy vaccination treatment and its complications.This form contains the written form of the information that is verbally explained to you, and will be stored in the hospital archives FOR USE IF A LEGAL REQUIREMENT OCCURS.As a result of the examination, it was decided that you / your patient should receive vaccine treatment. Your physician will give you the information written in this document before vaccination treatment, and you will finally make your decision on vaccine treatment on your FREE WILL.It is a LEGAL REQUIREMENT to sign EVERY PAGE of this form, by you and a relative of yours.1. Information about your disease:You have been diagnosed with allergic rhinitis after your examinations and tests. The vaccine treatment that will be applied to you can be in the form of injection into your arm, or in the form of drops or tablets taken by mouth.2. Who should be given the vaccine treatment, where, how and what should be considered:If vaccine treatment is administered in the form of injections, it will be administered to you by your physician or a nurse trained on allergy vaccines. Following the application of allergy vaccine, one or more of the following reactions can be seen; itching in the eyes, nose or throat, nasal congestion, runny nose, difficulty of breathing, cough, wheezing, dizziness, nausea, vomiting, rash, itching and shock. These reactions may rarely be severe or even fatal.If the vaccine is administered orally as a drop or tablet, mild itching or discomfort may be felt in the mouth. This complaint will usually go away spontaneously without treatment. Very rarely itching in the eyes, nose or throat, nasal congestion, runny nose, difficulty breathing, cough, wheezing, dizziness, nausea, vomiting, rash, itching and shock may appear. These reactions may rarely be severe or even fatal.After applying the allergy vaccine to you, you should wait in the hospital for at least 30 minutes. If you are under the age of 17, your parent or an adult with your legal responsibility should wait with you.APPROVAL OF THE PATIENT, PARENTS OR GUARDIANI am in my right mind and I believe I have the competency to make a decision. My doctor has made the necessary explanations about my condition. My doctor answered all my questions in a way that I can understand. I was informed about the side effects that may occur during vaccine treatment. In the event of a reaction during my treatment, I allow the healthcare personnel who apply my treatment to make any intervention.PATIENT, PARENTS OR GUARDIANName Surname: Identification number:Signature:Date:PATIENT’S RELATIVE or GUARDIAN’S RELATIVEName Surname: Identification number:Signature:Date:THE PHYSICIAN WHO OBTAINED THE INFORMED CONSENTStamp:Signature:Date:SIT is the only treatment method that can change the course of AR. When SIT was first used, it was administered subcutaneously . HoweverIt was concluded that it is highly effective in seasonal AR treatment and reasonably effective in the treatment of perennial AR due to mite hypersensitivity .It has been determined that uninterrupted long-term SCIT and SLIT provide clinical benefit. Both methods were found to be effective in seasonal and perennial AR treatment in reducing AR symptoms, however symptom control is better in seasonal AR. Its efficacy has been shown to be better in adults compared to children , 703.Key words: Allergen specific immunotherapy, subcutaneous, sublingual, seasonal, perineal, allergic rhinitis.1. Immunotherapy is effective in the treatment of AR patients.2. Prick test is preferred. In some cases, it is useful to test specific IgE.3. Immunotherapy should not be given to those with negative specific IgE tests.4. The patient should be evaluated in terms of different treatment options, and the treatment of the patient should be individualized.5. An informed consent should be obtained in terms of risks, benefits and cost of treatment, and the initial dose should be planned.6. Immunotherapy should be applied in places where its possible side effects can be treated. Treatment may be terminated if local or systemic side effects or complications appear.7. Maintenance therapy should be planned.8. Remission of disease is indicated by: No symptoms in the previous year, allergen prick test results as well as histamine reaction gets smaller by 50% compared to pretreatment, decrease in specific IgE levels, and a specific IgG level between class 3-5.Otorhinolaryngologists are responsible for the diagnosis, medical treatment and immunotherapy of AR.Immunotherapy methods are applied to selected patients who have clinically compatible AR symptoms and have Type 1 hypersensitivity reaction proven with the positive prick test and / or specific IgE.Otorhinolaryngologists are not responsible for the diagnosis of allergic conjunctivitis, asthma, dermatitis, which may be comorbid with AR. Again, they are not responsible for the treatment of these diseases with immunotherapy methods.Method: A literature search was conducted in Pubmed, Scopus, Google academic databases with the keywords “children, childhood, allergic rhinitis, treatment”. The meta-analyses were primarily reviewed until 2015. All international publications between 2015-2018 were included in the study. Older publications were used when sufficient data were not available in that period. Priority was given to meta-analyses and randomized controlled trials while making propositions. Other studies, expert committee reports and opinions of respected authorities have been used in the topics without any sufficient data in the literature.Keywords: Rhinitis, allergy, pediatric, treatmentAR is one of the most frequent chronic diseases in the childhood. Although the prevalence of AR varies in relation with the country and age, AR prevalence was found as 8.5% in children aged 6-7 years, and as 14.6% in children aged 13-14 years in the International Study of Asthma and Allergies in Childhood (ISAAC) study. In that study, the prevalence of AR was reported higher in Pacific Coast countries such as Australia, New Zealand, Korea, while lower prevalences were reported in Eastern Europe, and Central and South Asia . The epiAllergic rhinitis in childhood is a step of allergic march. Classically, atopic march begins with atopic dermatitis, and progresses to IgE-mediated food allergy, asthma, and AR . On the Although AR may be seen at any age, it is very rare to encounter AR in children under two years of age, since two or more seasons are required to develop hypersensitivity to aeroallergens. AR is usually evident after 3 years of age in children, and its prevalence increases with increasing age. In a prospective study on this subject, the prevalence of AR was found as 5% in children 4 years of age, and 14% when children got 8 years old. In fact, it has been shown that symptoms occur before the age of 20 in 80% of patients with AR .Established risk factors for AR are positive family history, male gender, being the first child of the family, early systemic antibiotic use, maternal smoking, exposure to indoor allergens, a serum IgE level above 100 IU / mL before 6 years of age, and presence of allergen-specific IgE. The children with food allergy or atopic dermatitis in early childhood have a high incidence of AR and asthma in the older ages. In addition, food allergy in infancy is an independent risk factor for development of AR and asthma , 708. AlEpidemiological studies performed in the previous decades revealed an increase in the prevalence and severity of allergic disorders. The results of these investigations paved way for the studies on the possible roles of predisposing factors on increased prevalence, such as diet, hygiene, infectious diseases, allergens, air pollution and other environmental factors. Whether the maternal food intake during pregnancy is related to the development of allergies in the child is a subject that is widely discussed in the literature. Beckhaus et al.  made a mSome researchers claimed that eating fish during pregnancy or in the neonatal period could prevent allergic diseases in the children, based on the assumption that polyunsaturated fatty acids can prevent the development of allergic diseases due to their anti-inflammatory effects. In their meta-analysis, Zhang et al.  reportedA number of studies investigated whether childhood vitamin D levels had any effect on AR development. Kim et al.  stated iEpidemiological studies have revealed a relationship between childhood antibiotic use and asthma and other allergic disorders. On experimental animal models, the effects of pathological or commensal bacteria on the immune system were examined, and it was shown that exposure to antibiotics directed the immune response towards type 2 inflammation, by altering the intestinal flora. Ahmadizar et al.  includedThe clinical pictures of AR may be different in children and in adults. Classical symptoms, such as recurrent sneezing, nasal congestion and rhinorrhea, which are more pronounced in adults, may be subtler in children. Children with AR often seek medical attention with complaints of recurrent sore throat and upper respiratory tract infections. Frequent sniffing, nasal discharge, itching in the eyes, nose and palate, postnasal discharge, chronic cough, weakness, fatigue and decreased appetite are other frequent symptoms . Facial AR has a number of comorbid conditions including asthma, allergic conjunctivitis, sinusitis, otitis media with effusion, frequent upper respiratory tract infections, dental disorders, obstructive sleep apnea, laryngitis and gastro-esophageal reflux.The coexistence of AR and asthma is frequent. AR and asthma progress like two phenotypes of a common basic condition. The presence of AR should be considered as a risk factor for asthma. Approximately 50% of patients with AR have asthma. On the other hand, up to 85% of asthmatics have AR. Treating AR symptoms in patients with asthma is important for asthma control. Children with AR should definitely be evaluated in terms of asthma due to this close relationship between asthma and AR , 714.Allergic conjunctivitis is characterized by itching, burning and watering in both eyes. Palpebral edema, chemosis and hyperemia are typical, and appear due to decreased venous return. Approximately 53% of the children with AR have concomitant conjunctivitis, and there is a correlation of the severity and duration of AR symptoms with the ocular symptoms in these patients . Since aNasal inflammation of AR may affect the ostiomeatal complex, and increase tendency for acute and chronic bacterial sinusitis. Positive skin tests have been shown in 54% of patients with chronic sinusitis symptoms. In another study, the frequency of AR diagnosed with skin tests was reported as 50-84% in patients who had sinus surgery. Although some authors find it reasonable that inflammation of AR triggers sinusitis, some authors do not agree. Taken together, epidemiological data show a relationship between sinusitis and allergy, but the role of allergy in sinusitis pathogenesis remains uncertain .The symptoms of AR and sinusitis are quite similar in pediatric patients. The classical symptoms of bacterial sinusitis are mucopurulent discharge, nasal congestion and cough. No symptom alone is sufficient to make the distinction between AR and sinusitis in pediatric patients. However, mucopurulent discharge and cough are the most useful symptoms for diagnosing sinusitis in children with AR .The relationship between otitis media with effusion (OME) and AR has been investigated in detail. It has been known that Eustachian tube dysfunction, inflammation and atopy play roles in OME etiology. Some studies indicated a higher OME prevalence in children with AR . It has AR has important consequences on children’s cognitive functions and quality of life. Chronic nasal congestion and associated sleep disorders lead to symptoms such as irritability, anxiety disorder, poor school performance and depression in children. Various studies suggested a relationship between attention deficit hyperactivity disorder (ADHD) and chronic rhinitis -721. In The diagnosis of AR is based on typical patient history, risk factors, classical symptoms and signs of the disease, and clinical testing of allergen-specific IgE. Although seasonal AR may often be diagnosed with the typical patient history, the history may not be sufficient alone in the diagnosis of perennial AR. The correlation between the responsible allergen and the symptoms may not be put forward in all patients, or children may not be able to express themselves adequately. Since the symptoms can be confused with recurrent upper respiratory tract infections in these children, patients should be evaluated for specific clinical signs of AR and comorbidities on physical examination. Mucosal edema, pale, bluish-nasal mucosa and clear rhinorrhea are seen on nasal examinations of allergic children, if they admit in the symptomatic period. A cobblestone appearance may be observed in the posterior pharyngeal wall and palate, which develops due to hyperplastic lymphoid tissue. In addition, some characteristic facial changes observed in pediatric patients with AR may help in the diagnosis. A transverse line may be seen in the supratip region of the nose, due to the fact that children repetitively rub their nose, which is called as “allergic salute”. The edema and color changes due to accumulation of hemosiderin  as a result of venous ponding around the lower eyelid, and Dennie-Morgan lines developing due to the contraction of the Muller muscle are characteristic physical examination findings observed in children with AR. In addition, facial anomalies and dental malocclusion due to chronic mouth breathing can be frequently encountered in children with AR , 718.Examination methods other than history, physical examination, skin tests and serum allergen-specific IgE are needed when the diagnosis is uncertain or when investigating the children for the comorbidities. Nasal mucociliary clearance and nitrous oxide measurement may be necessary in the differential diagnosis of primary ciliary dyskinesia. Nasal endoscopy and CT may be needed in case of nasal polyps, anatomical disorders and chronic sinusitis, and lateral radiographs can be used to diagnose adenoid hypertrophy .AR treatment in children includes environmental control measures, pharmacotherapy and immunotherapy, as in adults. However, factors such as patient and family education, patient compliance, medication side effects, and family concerns about adverse effects should be considered in this group of patients , 718.Avoiding allergens and symptomatic triggers is the first step in AR treatment. However, it is seldom possible to avoid allergens completely. Avoiding outdoor allergens is particularly difficult in children, and restriction of physical activities during the pollen season may lead to psychological problems. The studies investigated the effectiveness of avoiding pet and house dust mites failed to provide sufficient evidence on the effectiveness of avoiding these allergens. In their meta-analysis, Aroyeva et al.  concludePharmacotherapeutic principles of AR are similar in adults and children. However, the physician should be careful regarding the side effects of the medications in children. In addition, it is wise to choose the medications administered once or twice a day in order to improve treatment compliance in school-age children.Due to the limited benefit of environmental control measures, pharmacotherapeutics are usually necessary in children with moderate / severe or persistent AR. Treatment of AR with nasal corticosteroids, antihistamines or leukotriene modifiers is effective in reducing or controlling asthma symptoms .Systemic corticosteroids should be rarely used in children with AR due to their side effects, and presence of safer and more effective alternatives. Nasal corticosteroids (NCS) are highly effective in pediatric AR . They prThe potential effects of these drugs on growth and development should be taken into account when using NCS in children. Many authors have claimed that systemic absorption is needed for any effect on the hypothalamic-pituitary-adrenal axis and growth, and NCS have limited or no influence on the hypothalamic-pituitary-adrenal axis at the recommended doses -735. TheIn their meta-analysis, Mener et al.  analyzedIn conclusion, NCS should be administered to children in the smallest effective dose, the need for NCS should be re-evaluated periodically, and the children who use NCS for a long time should be followed-up for growth and development .The irritative side effects of NCS such as crusting, dryness and epistaxis may be minimized with the correct use of the medication and education of the parents.Histamine is one of the most important mediators of allergic reactions. Therefore, antihistamines are the first choice options in AR treatment. Antihistamines provide improvement in early phase reaction symptoms such as nasal itching, sneezing, rhinorrhea. The effect on nasal congestion is limited. First generation antihistamines  may cross the blood brain barrier owing to their lipophilic structures; leading to sedation, attention deficit, and even seizures. First generation antihistamines should no longer be used in AR treatment in children due to the risk of sedation and their other negative effects , 737. CeIn recent years, nasal antihistamines have been introduced. The nasal antihistamines in the market are azelastine and levocobastin. The efficacy and safety of azelastine has been demonstrated by multicenter studies. Grosman et al.  comparedMontelukast has been shown to be effective in pediatric patients with seasonal and persistent AR , 744. NeCromolyn sodium is a well-tolerated topical mast cell stabilizer with a weak effectiveness on nasal symptoms. It needs to be administered 4-6 times a day to exert its effect. It is also recommended to be used prophylactically before exposure to the allergen. Its disadvantages are its limited effectiveness compared to other classes of medications, and difficulty of administration 4-6 times a day in children. However, since they do not have serious side effects, and they can be used safely in children .Ipratropium bromide nasal spray is effective on rhinorrhea, but it is not effective on other symptoms of rhinitis including itching, sneezing and nasal congestion. Its side effects due to systemic anticholinergic effect are very rare. Local side effects may be seen including dry nose, dry mouth, and headache. It can be used in children when rhinorrhea is the main complaint . Nasal pThey reduce nasal edema by creating vasoconstriction and decreasing mucosal blood flow due to their sympathomimetic effects. Nasal decongestants are more effective than oral forms for relieving nasal congestion, and they have fewer systemic side effects. Vasoconstrictor decongestant sprays may be used for a short period to relieve severe nasal congestion in children, but long-term use may lead to rhinitis medicamentosa, characterized by rebound nasal congestion .It has been shown that nasal saline irrigation may be used as an adjunctive therapy in AR, and helps controlling symptoms by removing nasal secretions, allergens, and irritants from the nose . It contHermelingmeier et al.  performeOmalizumab is a recombinant human monoclonal anti-IgE antibody that binds to circulating IgE to prevent them from binding to surface receptors of mast cells and basophils. Kamin et al.  showed tSIT is based on the principle of administering allergens that cause symptoms in increasing doses to reduce the hypersensitivity to the allergen. Immunotherapy is indicated in children with AR who cannot be adequately treated with appropriate medical treatment methods . It is cSIT is traditionally administered by subcutaneous injections (SCIT). Different administration routes have been investigated due to difficulty of repetitive injections in children in children due to agitation as well as the risk of systemic allergic reactions. Allergens are administered into the sublingual tissues or the oral mucosa in SLIT, in the form of oral solutions or rapidly dissolving tablets.Larenas-Linnemann et al.  reportedKhinchi et el.  comparedIn conclusion, SLIT is a promising treatment method in the pediatric age group. However, randomized controlled clinical trials on larger series are needed due to the limited number of cases in the previous studies, and presence of data mostly on grass SLIT .Method: A total of 24 meta-analyzes were found in Pubmed database using the keywords ‘Allergic Rhinitis and aged and treatment’ and ‘Allergic Rhinitis and elderly and treatment’. Examination revealed that none of those were about the elderly population. A search with the keywords “Allergic rhinitis and geriatric and treatment” did not yield any meta-analyses either. Using the keywords ‘allergic rhinitis AND elder’, only 3 clinical studies were found between 2013 and 2018, however those were not performed on the elderly. A total of 15 studies were available between 2013 and 2018 with the keywords ‘ AND geriatric’.Keywords: Rhinitis, allergy, old age, geriatric, treatment.We included the full text articles specifically investigating the treatment of AR in the elderly. Bousquet et al. used a mIn parallel with medical and technological developments, the life expectancy and hence the elderly population is increasing. It has been supposed for a long time that skin prick test positivity is rare, there are changes in T/B lymphocyte ratios, decreased number of stem cells due to fatty degeneration in the bone marrow, lymph node regression, and decreased lymphocyte, macrophage and dentricitic cell functions in the elderly . It was Contrary to the traditional belief that allergic diseases are seen less frequently in the elderly population, it has been reported in recent years that the prevalence of allergies in the elderly population is 5-10% , and theDifferent and more complex clinical pictures may be seen on evaluation of elderly patients with allergic complaints due to the fact that these patients are not a homogeneous group, there are changes in the physiology with aging, and accompanying comorbidities may be present . For example, rhinorrhea in an elderly patient may be due physiological alterations in the elderly , old man’s drip as a result of decreased testosterone, mucosal atrophy, decreased mucociliary clearance, dehydration-mucous thickening, changes in external and internal nasal structures  , 771, asIn summary, diagnosis is the most important step of AR treatment in the elderly patients. However, due to the effects of the physiological changes mentioned above, some problems may be experienced in both in vitro and in vivo tests, and diagnosis can be difficult. For example, atrophy of the skin, altered vascular structure, sun damage, and cellular defects in allergenic responses may decrease test reliability, and prevent detection of atopy in skin prick tests , 764. KaAR treatment in the elderly aims to reliably and effectively relieve the patient’s symptoms and improve quality of life with three main methods, including allergen avoidance, pharmacotherapy  and immunotherapy. However, as mentioned above, the major problems in treatment of the elderly are the changes in drug metabolism, drug interactions, side effects of medications, comorbidities , difficulties in drug selection and insufficient data on these issues.In terms of the elderly population, patients are more exposed to indoor allergens due to restriction in activities and more time spent at home. Therefore, frequent cleaning of the house, changing used items, keeping animals away from home, cleaning carpets regularly, ventilating home by taking pollen changes throughout the year and during the day into account have been suggested. The patients with pollen allergy should not go out between 11 AM and 15 PM, and use HEPA filters in the living spaces. In addition, nasal moisturizing and nasal irrigation are also recommended due to dehydration, decreased mucociliary clearance and decreased nasal blood flow with aging. However, the evidence is insufficient in terms of cost effectiveness and applicability of these measures .One of the first-line treatments for AR in the elderly population is antihistamines due to their good oral absorption, and reaching an effective plasma level in as short as three hours. However, it has been known that the first generation antihistamines can easily cross the blood brain barrier due to their lipophilic structures, and cause sedation, confusion, anxiety and impaired cognitive functions. It has been also known that they can cause peripheral vasodilation and hypotension, urinary retention and constipation due to non-selective H1 receptor blockage, and they often interact with other medications. Therefore, they should be used very carefully in the elderly population . It is rThe new generation antihistamines are safe except for terfenadine and astemizole in presence of cardiac diseases, which is another comorbidity frequently encountered in the elderly . HoweverNasal azelastine may be used in seasonal AR treatment when oral medications cannot be used or response to treatment is inadequate since it has low risk of systemic side effects. Studies have shown that azelastine had equal efficacy to oral antihistamines such as ebastine, cetirizine, loratadine and terfenadine, it was easily tolerated in the elderly population, and effective on nasal congestion . In addiIn conclusion, oral or topical antihistamines can be used effectively and safely in the elderly, after evaluating liver and kidney functions, particularly in patients over 75 years of age. Dose adjustment may be necessary.Corticosteroids are recommended for seasonal and perennial AR in elderly patients, due to their anti-inflammatory properties and beneficial effects on all symptoms of rhinitis including itching, rhinorrhea and congestion . Small nDecongestants are effective in relieving nasal congestion, but they do not have any effect on sneezing, rhinorrhea and itching symptoms. Oral decongestants may cause problems such as palpitations, insomnia, hypertension and urination problems in the elderly population, and they are not recommended in presence of coronary artery disease, diabetes, hypertension, narrow-angle glaucoma and obstructive urinary disorders .The greatest risk of long-term use of nasal decongestant administration is the possibility of developing rebound vasodilation, nasal dryness, and rhinitis medicamentosa , 786. ThLeukotrienes play a key role in allergic mechanisms, and their receptor-level antagonists are preferred in the treatment of allergic diseases since they reduce inflammation, congestion, sneezing and rhinorrhea, and improve quality of life. Montelukast used as a monotherapy was shown to be less effective than nasal fluticasone propionate, but had similar efficacy with loratadine. However, combination of leukotriene receptor antagonists with antihistamines and nasal steroids provided much more control in seasonal and perennial AR compared to monotherapy . LeukotrCromolyn sodium provides mast cell stabilization as well as macrophage, eosinophil, monocyte and platelet inhibition, preventing release of inflammatory mediators and formation of both early and late phase allergic responses. However, it should be administered 4 times a day, and for about 3 weeks to show its beneficial effects. Therefore, it has no place in the treatment of acute attacks, however due to its safety and good tolerance, it is recommended for prevention of the symptoms in elderly patients who cannot tolerate antihistamines or other medications , 763.Although ipratropium nasal spray is used more frequently in nonallergic rhinitis, it can be considered as a treatment option in nasal discharge in the elderly population, refractory to other treatment options. It is not effective in other symptoms of rhinitis, and it has a good tolerance . It shouAnti IgE treatment reduces inflammatory response and is used as a promising treatment option. However, there is insufficient data for its use in the elderly population.It has been known that allergen specific immunotherapy (SIT) is the only treatment method that has the a longest-lasting effect in AR, and unlike other methods, may change the natural course of the disease. This treatment modality consists of administration of allergen in increasing doses until the maximal response is obtained, and maintaining this dose for 3-5 years. SIT was first administered through subcutaneous route (SCIT), then oral, sublingual (SLIT), nasal and bronchial routes have been used. SLIT has become popular and is frequently used in recent years due to ease of application and safety . SIT aimHowever, SIT has been mostly neglected in the elderly population, and patients aged 65 years or older were not included in the study group even in the randomized trials. Different recommendations are available for the elderly population in terms of SIT. The basis of these recommendations is the belief that allergy is rarely seen in elderly, changes in immune functions, and accompanying comorbidities in these patients, and SIT is neglected in their treatment plan. Although the studies are insufficient, some authors claimed that SIT was effective in the elderly as much as in the young people.In their review on management of allergic disorders in the elderly population, Ventura et al.  emphasizBozek et al.  performeBozek et al.  used SCIIn another placebo-controlled double-blind randomized study, Bozek et al.  investigAnother point to be considered in the application of immunotherapy in the elderly population is the applications in presence of comorbid conditions. In the literature, a number of conditions that are frequent in the elderly population have been identified as clinical contraindications of immunotherapy. Regarding this issue, Pitsios et al.  made a nAlthough some case reports described a link between SCIT application and autoimmune disorders, the authors did not find any evidence for that (level of evidence: III). There was no evidence that immunotherapy administration caused more frequent and serious side effects in cases with autoimmune disorders (level of evidence: IV), and there was no evidence that immunotherapy would be less effective in individuals with autoimmune disorders (level of evidence: IV). In line with these results, it has been stated that immunotherapy is considered to be relatively contraindicated in the remission period, and definitely contraindicated in the active period of an autoimmune disease, and immunotherapy should be used carefully in presence of autoimmune disorders since the data are insufficient (grade of recommendation: D).It has been stated that there is no information on the effect of immunotherapy on the course of the malignant diseases (NR), and that immunotherapy application is not expected to cause more frequent and more serious side effects (NR). It has been stated that immunotherapy is not expected to be less effective in presence of a malignant disease (NR). In line with these results, it has been reported that the application of immunotherapy in malignant diseases is considered as a definite contraindication (grade of recommendation: D).It has been reported that use of beta blockers is a relative contraindication for immunotherapy since they prevent performing an effective treatment in case of anaphylaxis due to inhibition of the effect of epinephrine on beta receptors, and unmet alpha adrenergic effect (level of evidence: III). More serious side effects were observed in those using beta blockers, however an increase was not expected in the frequency of side effects (level of evidence: III). There is no evidence showing that immunotherapy is less effective when the patient is on beta blocker treatment (level of evidence: III). Therefore, the authors pointed out that administration of immunotherapy in individuals using beta blockers must be decided on a profit-loss account, and SIT was considered as relatively contraindicated in the ones that use beta blockers (grade of recommendation: C).In case of use of ACE inhibitors, the authors stated that vasodilation caused due to their effects on the renin-angiotensin system might affect the response in anaphylaxis. Although it has been found that side effects may not occur more frequently, more serious side effects may occur in case of ACE inhibitor use (level of evidence: III). It was stated that there was no evidence for the effectiveness of immunotherapy (level of evidence: IV). In line with these results, the authors reported that there was no contraindication for immunotherapy in the ones that use ACE inhibitors (grade of recommendation: C).It has been known that epinephrine, which is used in case of an emergency situation can cause serious hypertension and cardiac arrhythmias in patients using monoamine oxidase inhibitors. However, there is no evidence that immunotherapy causes more serious and more frequent side effects in the use of monoamine oxidase inhibitors (level of evidence: IV) or that immunotherapy is less effective (level of evidence: IV). Therefore, immunotherapy is not contraindicated in patients using monoamine oxidase inhibitors. However, caution should be exercised while using epinephrine in these patients (grade of recommendation: D).There is no evidence that immunotherapy has a negative effect on the course of cardiovascular diseases (level of evidence: IV). There is no evidence that immunotherapy causes more frequent and more serious side effects, or immunotherapy is less effective (level of evidence: IV), however treatment of the side effects may be more difficult in these patients (level of evidence: IV). In the light of these results, the authors stated that the immunotherapy was relatively contraindicated in patients with cardiovascular disorders (grade of recommendation: D), and the decision for SIT should be based on obtaining expert opinion on cardiovascular disorder, careful evaluation of the disease and its treatment, anaphylaxis risk, and profit and loss assessment.There is insufficient evidence regarding immunotherapy in HIV positive states; the present data are based on the patients without serious symptoms. Immunotherapy has no negative effect on the course of the disease (IV), more frequent and more serious side effects are not expected (level of evidence: IV), and it is not considered that immunotherapy will be less effective (IV), however these remarks cannot be excluded (level of evidence: IV). Therefore, immunotherapy application is accepted as a relative contraindication in HIV positive patients, and it has been stated that the decision should be individually based (grade of recommendation: D).In general, immunotherapy has been reported to have a negative effect on the course of the disease in patients with immune deficiency or in need of an immunosuppressive therapy (NR), and theoretically it may increase the risk of more serious side effects (NR). In addition, immunotherapy is thought to be less effective in patients with adaptation problems and in patients with an impaired immune system (level of evidence: IV).There are no reported contraindications for immunotherapy in hepatitis B-C positive conditions. Since nodule formation is observed in patients with sarcoidosis after SCIT application, SLIT application is considered as a good alternative. Primary immunodeficiency states are considered as contraindications.In the light of these data, although the evidence level and the number of studies are insufficient, immunotherapy can be recommended as a useful, safe and successful method in the elderly population. However, additional care should be taken in terms of old age physiology, chronic diseases, multiple medication use and compliance of patients, and immunotherapy decision should be made on the individual basis .In conclusion, in order to provide effective treatment for allergic conditions that are thought to be increasing in the elderly, first the diagnosis should be made and the comorbidities  should be evaluated. Treatment methods applied in the elderly population, the success rates and reliability of these treatments are generally similar to the young population, but the most important point in planning treatment is the adaptation of patient-based treatment protocols and close follow-up of these patients.Method: Pubmed and Google Scholar databases were searched with the keywords “Pregnancy, Allergic rhinitis, Rhinitis, Diagnosis, Treatment, Medications, Safety, Drug effects, Perinatal outcomes, Breastfeeding, Lactation, H1-antihistamines, Corticosteroids, Leukotriene receptor antagonists, Decongestants”, in order to find the relevant papers on “treatment of allergic rhinitis during pregnancy and lactation”. The papers published between 1970-2017 were included in this review.Keywords: Pregnancy, allergic rhinitis, diagnosis, treatment, drug side effects, safetyAllergic diseases occur in approximately 20-40% of women of childbearing age, and 10-30% of pregnant women complain of AR and asthma . AR is uThe diagnosis of AR in pregnant women is made with a detailed medical history and symptom evaluation. If allergy testing has not been carried out in the past, in vitro tests such as allergen-specific IgE can be performed during pregnancy when necessary. Skin tests should not be performed during pregnancy, and postponed after delivery due to the risk of anaphylaxis .Treating AR in pregnant women is important for the health of the mother and fetus. Otherwise, impairment of nutrition, sleep and emotional well-being of the pregnant woman may have negative effects on the fetus .Balancing safety and efficacy of treatment is of paramount importance in the pregnant women . Almost Prescribing drugs to pregnant women is difficult and troublesome for clinicians due to the lack of evidence-based information. FDA  risk categories should be taken into consideration in prescription of medications during pregnancy  CategoryThe general principles of AR treatment in pregnant women are not different from the treatment of non-pregnant women. Avoidance of allergens and irritants is the first step, before pharmacotherapy . Nasal sNasal corticosteroids (NCS) are the drugs of choice for AR treatment due to their good efficacy and pharmacokinetic properties . The onlNCS have been recommended as the first choice agents in AR treatment during pregnancy, especially after the first trimester , 810. SiSystemic corticosteroids are not usually necessary in AR treatment in pregnant women . The risA number of studies have shown safety of both first and second generation antihistamines during pregnancy, including the first trimester . A recenMost pregnant women with indication for antihistamines for AR are properly treated with second generation antihistamines since these agents cause sedation less, and they have less cholinergic side effects compared to first-generation agents . Among tAzelastine is not recommended during pregnancy as minor fetal side effects are observed in animals, and data on its safety are not available in humans .A new combination of fluticasone propionate and azelastine has been marketted. There are no studies in the literature regarding its use in pregnant women. It may be advisable to consider the measures applied for both components.Due to its excellent safety profile during pregnancy, nasal cromolyn sodium may be considered as a first-line treatment in mild AR (806). It is the safest drug recommended in the first trimester of pregnancy , 818. HoHigher risks for gastroschisis -822 abd, 823, enSince the safety data for systemic decongestants during pregnancy are insufficient, they are not recommended particularly in the first trimester . After tAlthough side effects of topical ipratropium are rare, there are no studies in the literature regarding nasal use during pregnancy.The available data for use of montelukast in pregnancy has mostly been obtained from studies on pregnant women with asthma -831. TheThe safety of allergen specific immunotherapy in pregnancy has been demonstrated by many authors. The first study on SCIT during pregnancy dates back to 1978. In this study, Metzger et al.  studied The maintenance therapy can be continued during pregnancy if the patient gets pregnant during immunotherapy, but the dose should not be increased . TerminaSome authors have suggested that immunotherapy can prevent allergic sensitization of the child as well as improving the allergic condition in pregnant women , 836, buAlmost all medications pass into breast milk with passive diffusion. The higher the plasma level, the greater the transition into breast milk. However, this amount is usually less than 2% of the dose taken by the mother. In addition, many agents cannot be absorbed from the gastrointestinal tracts of the infants, and clinically effective levels are rarely achieved , 837. ItSimilar to pregnancy, it will be appropriate to use the lowest drug dose that is effective for controlling rhinitis symptoms, and for the shortest time during breastfeeding. Topical medications have the advantage of low systemic bioavailability, and are less likely to pass into the breast milk. The medication should be taken immediately after breastfeeding in order to decrease the dose reaching the baby whith breastmilk. In addition, it should be advised that the mother should be informed about the toxicity symptoms of the medication in the baby. For example, irritability can be seen in the baby with a decongestant taken from the breast milk .Many drugs used in the treatment of AR  on children with seasonal AR due to parietaria pollen, and intermittent asthma. They investigated relief of nasal symptoms and the impact on quality of life. The active treatment group was administered Bifidobacterium mixture, mixed in a small amount of water or milk, once a day for 8 weeks. Cetirizine syrup and salbutamol inhaler were given as rescue therapy. The patients were asked to note the doses and the days when they used rescue medications. The patients’ total nasal symptom scores (TNSS) and Mini Rhinoconjunctivitis Quality of Life Questionnaire (Mini-RQLQ) scores were recorded at the beginning and end of the treatment. It was found that TNSS decreased significantly in the treatment group, and increased significantly in the placebo group. In terms of quality of life, it was reported that probiotic use significantly improved symptoms compared to placebo. Both groups used similar amounts of rescue medications. There was no difference between the two groups in terms of treatment compliance and side effects.Miraglia Del Giudice et al.  performe9 colony-forming units / capsule) administration for 8 weeks in the allergy season. They employed Mini-RQLQ, and measured total IgE and Treg cells in 173 patients with seasonal AR. They found significant improvements in the global scores as well as subgroups of activity, nasal, and other symptoms in the probiotic group when compared to placebo group, however there was no difference between the groups for ocular symptoms. There was less constipation in the probiotic group, however the difference between two groups reached statistical significance in 3rd, 4th, 6th, and 7th weeks. The total IgE levels and Treg values were measured at the baseline and in 6th week, there was an increase in both levels in 6th week compared to baseline in the probiotic group, however the difference between two groups was not significant.In a randomized placebo-controlled double-blind study, Dennis-Wall et al.  investig9 CFU), SLIT + Vitamin D (1000 IU), SLIT + placebo (0.3 mg Lactose) and allergic rhinoconjunctivitis patients that were not administered SLIT. The authors followed up patients for 5 months. SLIT + placebo group did not show any differences from the control group except for symptom-medication scores and FEV1%VC values. In SLIT + Vitamin D group, FEV1% VC as well as CD4+ CD25+ Foxp3 +, TLR values increased, and symptom-medication scores decreased significantly compared to the control group, independent of serum vitamin D levels. In SLIT + probiotic group, CD4 + CD25 + Foxp3 +, FEV1% VC, serum vitamin D levels increased, TLR positive cells, respiratory nitric oxide levels and symptom medication scores decreased more than the Vitamin D group. There was no significant difference between pre- and post-treatment measurements of other investigated immunological parameters. The authors claimed that adjuvant Vitamin D and probiotics might have directly induced Fox3P3 cells and enhanced the immunological effects of SLIT, and the results of their study provided a direct evidence for complementing SLIT with probiotics and vitamin D to application as might be recommended.A new area for use of probiotics is immunotherapy. In recent studies, combination with biological agents has been attempted in order to increase the success of immunotherapy, and successful results have been obtained. Tang et al.  were theth week of gestation and 3 months postpartum to 415 pregnant women, followed their children for 6 years, and studied development of atopic dermatitis, asthma, and allergic rhinoconjunctivitis in their children in a prospective randomized placebo-controlled double-blind trial. The authors aimed to show the preventive effect of early use probiotics in childhood on atopic dermatitis development, which was shown in previous studies, and also to investigate the effect of perinatal probiotic use on the formation of allergic disorders in the general population, rather than the atopic population, which was not shown before. The pregnant women included in the study were administered daily 5 × 1010 colony-forming units (CFUs) Lactobacillus rhamnosus GG (LGG), Bifidobacterium animalis sub sp. lactis Bb-12 (Bb-12) and 5 × 109 CFU L. Acidophilus La-5 (La-5) in 250 mL of low-fat fermented milk. Control patients were administered probiotic-free milk with a similar taste, and the children were not given any probiotic supplements. Clinical follow-up of the patients was made at the ages of 1, 2 and 6 years, presence of disorders were recorded, and skin prick test was performed and allergen-specific IgE levels were measured. At the end of the study, the authors concluded that the use of perinatal probiotics did not cause any change in the incidence of cumulative allergic rhinoconjutivitis, asthma and atopic sensitization prevalence at the end of the 6th year.Simpson et al.  administCosta et al.  made a rth and 12th weeks in all participants. The use of levocetirizine as a rescue medication between 8th and 12th weeks significantly decreased in both groups. Although nasal, throat, ocular and total symptom scores decreased significantly in both groups during the follow-up period, no significant differences were found between two groups in terms of these values. There were significant improvements in general RQLQ scores in both groups during follow-up, but there was no statistically significant difference between the groups. Detailed analysis of symptom scores revealed a significant decrease in the symptom scores in the 5-8 and 9-12 weeks in the probiotic group, however this decrease was not evident in the placebo group. The analysis of RPQLQ subgroup scores between baseline and 12th week showed significant improvements in the probiotic group compared to placebo only in the nasal itching, sneezing and swelling of the eyes domains. There was no difference between the groups in terms of cytokine values.Lin et al.  examined9 CFU LcS or placebo for 4 weeks, and the baseline and outcome values were compared. There was no difference between the baseline and post-nasal allergen provocation test in TNSS, nasal peak flow, asthma or spirometry measurements values in the patients. Nasal lavage analysis did not reveal any difference in terms of eotaxin, IL-13, IL-4, IL-5, MIP-1α or RANTES. No significant change was detected in sIL-1RI, sTNFR1, sCD30 or sIL-4R in nasal cultures. There was a significant change between pre- and post-provocation IL-1b levels in the control group, but not in the probiotic group. In contrast to these findings, there was a significant difference in the probiotic group in terms of sIL-1RII, however there was no difference in the control group. Nasal cell cultures showed less CD86 and CD86 + CD252 + expression after allergen challenge in the control group compared to the treatment group. In peripheral blood cultures, no significant difference was found regarding IL-4, IL-5, IL-10, IL-12, IL-13, MIP-1 alpha eotaxin, RANTES or TNF-alpha. The authors reported that IFN gamma increased in the treatment group after provocation, and TGF beta, which was initially high in the control group, was not high anymore following provocation. The examination of peripheral blood cells in terms of systemic response showed no difference in terms of sCD23 after nasal provocation, whereas significant sCD23 release was detected in the control group after in vitro pollen application. There were no significant differences in terms of IgG, IgG4 and IgE. In summary, the authors showed changes in some immunological parameters, however this was not correlated with any change in the clinical parameters.Ivory et al.  investigEscherichia coli strain Nissle 1917 (EcN) (2.5–25 x109 CFU) on 30 patients aged 18-65 years with grass allergy, starting administration two months before the allergy season, and going on for 6 months. The patients were examined clinically with symptom medication score as the primary outcome, and skin prick test, conjunctival provocation test, RQLQ and compliance with treatment as the secondary outcomes, however no significant differences were found between placebo and probiotic groups. It was found that compliance with treatment was good. Total and grass-specific IgE values were examined as immunological parameters, and no significant differences were found between the groups. It was shown that specific IgA increased significantly in the treatment group.Dölle et al.  performeThe use of probiotics in treatment of allergic rhinitis is shown on A literature search in the Turkish Medical Database did not yield any publications.In conclusion, probiotic use has been considered a promising treatment method. However, the use of different probiotic formulations, the problems in designs of the studies, and the difference in evaluation criteria make it difficult to make a clear evidence-based interpretation on the use of probiotics. Therefore, routine use of probiotics is not recommended for AR treatment, since the available evidence is derived from insufficient and heterogeneous studies.Method: A literature search was conducted in Pubmed, Scopus, Google academic and Thomson Reuters databases with the keywords “phototherapy, allergic rhinitis, rhinophototherapy, endonasal phototherapy”. Only meta-analyses were taken into consideration among the papers published before 2015. All international publications were included in this review between 2015 and 2018. There were 20 articles published in the international literature between 2013 and 2018. After reviewing the summaries of the articles, the articles that were not directly related to the keywords of phototherapy in AR were eliminated, and 10 research articles and one meta-analysis remained. Since four of these research articles were analyzed in the meta-analysis, the tables and graphics of this study were not included in the tables and graphics again. At the end, one meta-analysis and 6 international publications were included in this review. National literature was searched through Ulakbim and Google academic databases with the keywords “ fototerapi, alerjik rinit, rinofototerapi” without any date restrictions, and, three clinical research articles were identified.Ancient Egyptians and Romans benefited of the therapeutic effects of sunlight thousands of years ago. With the advancements in modern medicine, phototherapy devices producing ultraviolet (UV) light have been used in order to benefit from the immunosuppressive and anti-inflammatory effects of different wavelengths of UV light, particularly for treatment of the dermatological conditions. Recently, rhinophototherapy devices have been developed for intranasal use. Rhinophototherapy devices have been launched in a number of countries, and they appear as an emerging alternative treatment method in the treatment of patients with AR.Cho et al.  conducteBella et al.  investigAlyasin et al.  conducteTatar et al.  includedThe therapeutic effect of UV light is mainly linked to its immunosuppressive and immunomodulating effects. The leading mechanism that explains the immunosuppressive effect of ultraviolet light is induction of apoptosis. It has been suggested that this effect of UV radiation induces DNA damage . PossiblKitamura et al.  investigHistamine is one of the main mediators in allergic reactions, and it shows its effect through H1 receptors. H1R is directly related to the occurrence of symptoms in allergic reactions, and it is considered as a rate-limiting receptor. Increased H1R mRNA expression has been shown in patients with AR. Therefore, it was supposed that treatment methods that could decrease H1R gene expression in the nasal mucosa might be beneficial in treatment of AR. In an experimental study, Kitamura et al. demonstrated that nasal low-dose 310 nm narrow band-UVB application suppressed the upregulation of the H1R gene, but it did not induce apoptosis. This effect was not observed at wavelengths longer or shorter than 310 nm. According to the results of that study, the authors suggested that 310 nm narrow-band UVB phototherapy might lead to improvement of AR symptoms, independent of apoptosis .Yıldırım et al.  investigNational literature on the use of phototherapy in AR treatment includes Demirbaş et al.’s  study, ith month. The authors stated that nasal symptoms, restricted activities and sleep parameters improved the most in the short-term, however, ocular and non-allergic symptoms improved minimally. The authors concluded that phototherapy improved AR symptoms and examination findings, and affected quality of life scores favorably in the short-term, however these favorable effects decreased gradually in the long-term.Yaz et al.  investigIn a retrospective study, Akdağ et al.  investigWhen the results of studies on the effectiveness and safety of phototherapy in AR treatment are assessed, one may say that it improves AR symptoms and quality of life in the short term. One-session phototherapy was well tolerated without any obvious adverse effects except mild nasal dryness, which resolved in a few days .Almost all of the studies in the literature compared improvement in symptoms and quality of life before and after a single-session phototherapy. However, no information was given about the long-term results. Only one study in the literature followed up patients for one year after phototherapy, and Ayaz et al.  reportedAbsence of multicenter, randomized, double-blind, controlled studies is an important shortfall for rhinophototherapy .The measurement methods used in the vast majority of studies in the literature are not based on objective data such as nasal airflow and inflammatory mediators. Therefore, the mechanism of action of phototherapy in AR treatment is not fully known. In the prospective, randomized double-blind single study related to the subject, objective data including nasal mucociliary clearance measurement, objective smell tests, nasal inspiratory peak flow rate, and nasal epithelial ICAM-1 expression were investigated . HoweverIn conclusion, results of short-term rhinophototherapy are promising. However, there is not enough data on its long-term efficacy and safety. There is a need for multicenter, randomized controlled studies on long-term follow-up of the patients.Keywords: Phototherapy, allergic rhinitis, rhinophototherapy, endonasal phototherapy.Method: The international literature was searched with keywords “nasal secretion, Botulinum toxin, allergic rhinitis treatment” in Pubmed, Scopus, Google academic and Thomson Reuters databases. All international publications were included in the study between 2013 and 2018. In the literature review, 15 articles were identified in the international literature published between 2013 and 2018. After reviewing the abstracts of the articles, the articles that were not directly related to the keywords of “botox in allergic rhinitis” were eliminated, and four research articles and two meta-analyzes were taken into consideration. Two research articles published before 2013 were also taken into consideration since they were directly related to the subject. At the end, two meta-analyzes and six international publications have been included in this report. National literature was scanned in Ulakbim and Google academic databases with the keywords “ nazal sekresyon, Botulinum toksini, alerjik rinit tedavisi” without any restrictions on the date of publication, and one clinical research article was found. It was not included in this report since its publication date was very old.Clostridium botulinum, an anaerobic bacterium  are placed into the nasal cavity, and left there for about 30 minutes. Gel form  or nasalAbout 40-200 U of botox may be used for infiltration. The amount of botox units is controversial. Nasal septum, inferior turbinate and middle turbinate were mostly preferred for infiltration.Since the nasal septal blood flow is richer than the turbinate blood flow, the effect of the nasal septal injections lasts longer .The leveThe most commonly used method for dilution in topical and infiltration is 100 U botox diluted with 2.5 mL of saline, 1 mL of this solution contains 4 U botox. One study carried out on this subject suggested injection of 12.5 U of botox to bilateral posterior nasal walls, and reported an improvement in AR symptoms for 2-4 weeks .The effect of botox infiltration usually becomes evident on the 3rd day after injection. The maximum effect occurs in the 2nd week. The beneficial effect ends after 3-6 months. The toxic dose is 2500-3000 U .Dryness and epistaxis have been reported as adverse effects.A review on this subject included 16 studies conducted between 1998 and 2015. In those studies, botox injection dose was 8-60 U, and botox-impregnated sponges contained 20-100 IU of botox. The injection site was generally inferior turbinate, middle turbinate and nasal septum. Rare adverse effects included epistaxis and nasal dryness. The maximum duration of action was reported as 20 weeks .Animal experiments with botulinum toxin applications showed that nasal secretions and allergy findings decreased in 3 days after botox applications .In conclusion, nasal botox application is an expensive, short-term effective, but easy and safe alternative treatment for AR. The level of evidence is IIb and grade of recommendation is B.Keywords: Nasal secretion, botulinum toxin, allergic rhinitis treatment.Category of evidenceStrength of recommendationNational publicationsNo articles were found matching ART-KLVZ-2.1 criteria.Appendix-2. Table of the references.The level of evidence and grade of recommendation columns were added to this table.In addition, it was stated whether the related pharmaceutical company had financial support in the studies.Some articles were deemed necessary to be included, but their full text could not be found. This was stated in an additional column, and these studies were included in the review due to the small number of publications on the subject.