Todays post will briefly cover the history of allergic rhinitis, the function of the nose, the pathophysiology of allergic rhinitis, the medical therapy available and the clinical study I participated in comparing the as needed use of an oral antihistamine versus an intranasal steroid for the treatment of allergic rhinitis.
 
Skin testing for inhalant sensitivities was introduced in 1873 by Charles Blackley.
C.E. Benjamins was the first otolaryngologist to appreciate the importance of allergy in this specialty. He is most noted for his work in the Dutch Indies in the 1920s pertaining to diseases of the nose. First generation antihistamines were first introduced in 1937 but were not widely available in the U.S. until 1946. Second generation antihistamines were first introduced in 1987. These are the non-sedating antihistamines. Nasal steroids and nasal anti-cholinergics are the most recent therapy introduced. The nose functions as an airway, as a sensory organ, as a source of humidification, as a filtrating device, as a source of muco-ciliary transport and as a resonator.

Rhinitis is an inflammation of the mucous membranes of the nose. Characteristic nasal symptoms include congestion, sneezing, itching, postnasal discharge, and rhinorrhea. Rhinitis can be allergic, non-allergic or both. When classifying rhinitis, allergic rhinitis can be classified as seasonal, perennial, episodic or a combination of all the above. Non-allergic rhinitis can be infectious in both the acute and chronic setting, can be non-allergic with eosinophilia syndrome, can be perennial non-allergic rhinitis, which is a vasomotor response, and can be induced by other factors including hormones, exercise, drugs or occupational exposure. Conditions that may mimic rhinitis include inflammatory conditions, Wegeners granulomatosis, sarcoidosis, lupus, Sjorgrens syndrome or nasal polyposis. Structural or mechanical symptoms that may mimic allergic rhinitis include a deviated septum, hypertrophic turbinates, adenoidal hypertrophy, foreign bodies or nasal tumors.
When looking at the distribution of rhinitis we see that 43% of all rhinitis is allergic while 23% is pure non-allergic and the remaining 34% are a combination. The impact of allergic rhinitis on a community is great. It affects approximately 20 to 40 million people annually, and is the fifth most common chronic illness. It is the most prevalent chronic illness condition in patients under 18 years of age. It affects both the physical and mental health status of individuals and approximately 3.8 million days of both work and school are lost annually. The direct costs of allergic rhinitis are approximately 2.7 billion dollars a year.

Risk factors for allergic rhinitis include a family history of atopy, serum IgE levels greater than 100 before age six, higher socioeconomic class and exposure to indoor allergens such as animals or dust mites. The natural history of rhinitis includes an onset that is common in childhood, adolescence or early adulthood. Symptoms often wane in older adults but may develop or persist at any age. There is no apparent gender selectivity or predisposition and allergic rhinitis may contribute to other conditions including sleep disorders, fatigue or learning problems.
The allergic response is a complex allergy driven mucosal inflammation including a number of inflammatory cells, mediators and cytokines. There is an early phase response, a late phase response and a priming response. The initial response is an allergen, such as pollen, being presented to the nasal mucosa. This allergen is recognized as an antigen by an antigen-presenting cell and presented to plasma cells. These cells subsequently produce IgE and attach themselves to mast cells awaiting re-exposure. Upon re-exposure, an antigen antibody complex is formed and the mast cell degranulates. During degranulation, histamines are released, leukotrienes, platelet activating factor as well as other factors. While certain nasal mediators such as histamine are responsible for the early phase reaction, which includes patient symptoms such as sneezing, rhinorrhea and congestion, additional nasal mediators are released including the cytokines, IL4 and IL5 which result in recruitment of additional cells to the nasal mucosa. These cells include Eosinophils, additional mast cells and basophil cells. It is this environment which sets up the hyper-responsiveness of the nasal mucosa as well as priming of the nasal mucosa.
When evaluating a patient with allergic rhinitis, history and physical exam are the two most important steps. Allergy skin testing is available as well as nasal endoscopy and nasal cytology. Neither total serum IgE nor total circulating eosinophil counts are indicated in evaluation of allergic rhinitis.
When managing patients with allergic rhinitis, four general principles of management should be considered. First and foremost, avoidance of factors that cause symptoms. Second, the use appropriate treatments. Third, evaluation of the patient for immunotherapy if these treatments are unsuccessful and fourth, education of the patient and close follow-up.
Environmental control measures include keeping windows and doors closed during the allergy season, reducing outdoor activity during high pollen days, maintaining a dust free, allergen free environment, keeping pets outdoors, avoiding smoke and strong odors and
using air conditioning and/or air filters. Allergen immunotherapy may be highly effective in controlling symptoms of rhinitis. Candidates should be selected based on their severity of symptoms, failure of other treatment modalities and the presence of co-morbid conditions. Selection of immunotherapy extract should be based according to the specific IgE antibodies.
Pharmacotherapy available for allergic rhinitis is vast. Over the counter treatments include intranasal cromolyn sodium, intranasal decongestants, intranasal saline, oral antihistamines and oral decongestants. Prescription treatments are also available including intranasal and systemic antihistamines, systemic decongestants, intranasal and systemic corticosteroids and intranasal anticholinergics.
Sudafed costs approximately $20.00 for 30 days. Nasalcrom is approximately $16.50 and Atrovent is approximately $24.00 for a 30-day treatment. Second generation antihistamines are by far the most expensive, with Claritin being the most expensive and Zyrtec and Allegra not far behind. Placing patients on multiple drug therapies can be a financial burden to them.
Pharmacotherapy guidelines should be dictated by efficacy, cost and patients motivation and should be individualized based on severity of symptoms. Typical mild disease is treated with an oral antihistamine and moderate to severe disease is typically treated with a nasal steroid, either alone or in combination with another agent. The delineation between mild and moderate to severe disease is typically the need for use of medication daily.
The second half of this presentation will be a clinical study that I participated in at Dr. Robert Naclerios lab at the University of Chicago. This data was presented in abstract form at the American Academy of Allergy, Asthma and Immunology this year and is currently in submission to the Journal of Clinical Immunology. The purpose of the study was to compare the effectiveness of an as needed use of an H1 antihistamine or an intranasal steroid in the treatment of seasonal allergic rhinitis. We conducted a randomized parallel group study with 88 subjects with a history of ragweed allergic rhinitis and a positive skin prick test during the 1999 ragweed season. Subjects were randomized to receive Flonase or Claritin on an as needed basis once a day according to their symptoms. Outcome measures included the rhinitis quality of life questionnaire (RQLQ), daily symptom diary scores and number of eosinophils counted by two separate observers and the level of eosinophilic cationic protein in nasal secretions obtained by nasal lavage on each of three visits. The RQLQ is a clinical outcome measure that has been proven by Juniper and associates and has seven domains. These include sleep, practical problems, nasal symptoms, eye symptoms, emotional and activity. The average score for each domain is computed and the overall quality of life is the average of these seven domains. The lower the score the better the quality of life. Each patient recorded their symptoms for rhinorrhea, nasal congestion and a composite of other symptoms in a diary twice a day. They were instructed to rate their symptoms on a scale of zero to three, with zero being no symptoms and three being the most severe. The total symptom scores were then added up and analyzed for each day. In addition, the patients were asked to note in this diary if they used the medication during the day and which day they used it. Eosinophil counts were obtained by taking a nasal lavage on each of three visits to the clinic. The patients were asked to sit in a chair and approximately 10 ml of normal saline was introduced into the nasal cavity. They then held their head back for 10 seconds and then brought their head forward again and the sample was recollected. This sample was then shaken and placed in the hemocytometer and a total cell count was obtained. Each sample was then placed on slides and stained to be counted. Eosinophilic cationic protein (ECP) was measured using a supernate decanted from the sample obtained. A double antibody radioimmuno assay was used to compare each sample to a standard curve and determine the overall levels of ECP.
The treatment period was over four weeks during the 1999 ragweed season. On Day one the patients were randomized, filled out an RQLQ and nasal lavage was obtained. On Day two the symptom diaries for 14 days were received. The patients again filled out an RQLQ and nasal lavage was obtained. On the final visit, Day 28, the symptom diaries were again received. The RQLQ was filled out and nasal lavage was finally taken.
The demographics of our patients matched well. There were 42 patients in both the Claritin group and the Flonase group. Their ages were approximately the same. The sex was approximately the same. Race was similar and the skin wheal tests were similar.
We found that the Claritin group used their medications ranging from Day 5 to Day 28, with a median usage of 18 days. The Flonase group used their medication anywhere from 3 to 28 days with a median use of 17. We compared the RQLQs of the Flonase group on visit two and visit three to their first initial visit. We found a statistically significant decrease, meaning an improved quality of life in the activity, sleep, practical, nasal, the second vision of eye and the overall domains. These results were not duplicated and there was no difference found in the Claritin group. Both the Flonase and Claritin groups had very similar RQLQs on visit one, but on visit two and visit three, the Flonase RQLQs improved, while the Claritin RQLQs remained unchanged. At the beginning of the study both the Claritin group and the Flonase group had very similar sympton scores but ranging from Day six to approximately Day 28 the Flonase group had improvement in their symptoms scores while the Claritin group remained unchanged or slightly worse. The median 28 day score for the overall Flonase group was 4.0 and that for Claritin group was 7.
The number of Eosinophils on visit two and visit three decreased as compared to visit one for the Flonase group and this was statistically significant. Additionally, the number of Eosinophils in the Claritin group increased on visit two and visit three. When doing a post ad hoc analysis comparing the Flonase group to the Claritin group, we also found a significant decrease in the number of Eosinophils. The levels of ECP protein followed a similar trend while on visit two and visit three the levels of eosinophilic cationic protein decreased in the Flonase group. It increased on visit two in the Claritin group and showed a similar trend in visit three. In addition, when comparing the two group, the Flonase group showed a statistically significant decrease in the levels of ECP protein. When correlating the number of Eosinophils to the ECP protein we found a correlation coefficient of approximately 0.7 with a P value of 0.01.
When patients experienced sneezing, runny nose, itchy nose and congestion, these are all the results of nasal mediators. Although histamine is one nasal mediator, there are many others involved in allergic response including Tryptase, prostaglandin, leukotrienes, cytokines and chemokines. These are released by mast cells, basophils, T-lymphocytes, neutrophils and Eosinophils. Nasal steroids act early in their allergic response and block the action of these inflammatory mediators thus decreasing patient symptoms. This is the pathophysiological explanation for the results of our study.
In summary, we believe our study was the first to show the superiority of an intranasal steroid used as needed compared to an oral antihistamine for the treatment of allergic rhinitis. The size of subjective outcome measures including the RQLQ and symptom diaries suggests a clinical as opposed to a mere statistical difference between the treatment groups. In addition, objective outcome measures provide a pathological explanation for our results. Intranasal steroid used as needed in subjects in seasonal allergic rhinitis resulted in improved quality of life, significant improvement in symptoms as compared to oral antihistamine and significant reduction in nasal Eosinophils and ECP levels during the ragweed season. In conclusion, we felt that as needed intranasal steroids are more effective than an oral antihistamine in the treatment of seasonal allergic rhinitis.