- Email: [email protected]
Examination, diagnosis and classification for Japanese allergic rhinitis: Japanese guideline
Auris Nasus Larynx 39 (2012) 553–556
Contents lists available at SciVerse ScienceDirect
Auris Nasus Larynx journal homepage: www.elsevier.com/locate/anl
Examination, diagnosis and classification for Japanese allergic rhinitis: Japanese guideline Shigeharu Fujieda a,*, Yuichi Kurono b, Kimihiro Okubo c, Keiichi Ichimura d, Tadao Enomoto e, Hideyuki Kawauchi f, Keisuke Masuyama g, Minoru Goto c, Harumi Suzaki h, Yoshitaka Okamoto i, Hiroshi Takenaka j a
Department of Otolaryngology – Head & Neck Surgery, University of Fukui, Fukui, 23-11 Shimoaizuki, Eiheiji-Matsuoka-cho, Yoshida-gun, Fukui 910-1193, Japan Department of Otolaryngology – Head & Neck Surgery, Kagoshima University, 8-35-1 Sakuragaoka, Kagoshima 890-8520, Japan c Department of Otorhinolaryngology, Nippon Medical School, 1-1-5 Sendagi, Bunkyo-ku, Tokyo 113-8603, Japan d Department of Otolaryngology – Head & Neck Surgery, Jichi Medical University School of Medicine, 3311-1 Yakushiji, Shimotsuke, Tochigi 329-0498, Japan e NPO Japan Health Promotion Supporting Network, 3-68 Komatsubaradori, Wakayana, Wakayana 640-8269, Japan f Department of Otorhinolaryngology, Shimane University, 89-1 Enya-cho, Izumo, Shimane 693-8501, Japan g Department of Otorhinolaryngology, University of Yamanashi, 1110 Shimokato, Chuo, Yamanashi 409-3898, Japan h Department of Otorhinolaryngology, Showa University, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo 142-8666, Japan i Department of Otolaryngology, Head and Neck Surgery, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8670, Japan j Department of Otorhinolaryngology, Osaka Medical College, 2-7 Daigaku-cho, Takatsuki City, Osaka 569-8686, Japan b
A R T I C L E I N F O
A B S T R A C T
Article history: Received 30 August 2011 Accepted 13 January 2012 Available online 7 March 2012
Many countries throughout the world have experienced an increase in the prevalence of allergic rhinitis (AR), which has come to be a major cause of morbidity in developed countries. The pathology underlying AR is regarded as IgE-mediated type I allergy characterized by mucosal inflammation that occurs in response to allergen exposure. In Japan, AR caused by Japanese cedar pollen, the most common allergic disease, has become a salient public health challenge. Almost all primary care physicians and otorhinolaryngologists have been consulted by AR patients between February and April. Although most such patients have received treatment, numerous patients with AR have not received proper examinations for AR. Clinical guidelines are systematically developed statements that are designed to help practitioners make decisions about appropriate and effective health care. Guidelines in many countries including Japan have been published for AR. Unfortunately, those guidelines have remained untested. Moreover, they might be difficult for non-specialists to use. In this review, we specifically examine the present standard examination for diagnosis of AR and optimal classification for AR in Japan. We hope that this review would be used not only for the support of daily practice but also for selection of AR patients for clinical trials. ß 2012 Published by Elsevier Ireland Ltd.
Keywords: Japanese cedar pollen Guideline Perennial allergic rhinitis Seasonal allergic rhinitis
1. Introduction Allergic rhinitis (AR) is a type I allergic disease on nasal membranes. In principle, it is associated with sneezing, rhinorrhea, and nasal congestion as its major three symptoms. Allergic rhinitis and its Impact on Asthma (ARIA) recommended that AR is divided into ‘intermittent’ or ‘persistent’ [1]. Intermittent signifies that the symptoms are present for less than 4 days a week or for less than 4
* Corresponding author at: Division of Otorhinolaryngology – Head & Neck Surgery, Department of Sensory and Locomotor Medicine, Faculty of Medical Science, University of Fukui, Shimoaizuki, Matsuoka, Eiheiji-cho, Yoshida-gun, Fukui 910-1193, Japan. Tel.: +81 776 61 8407; fax: +81 776 61 8118. E-mail address: [email protected] (S. Fujieda). 0385-8146/$ – see front matter ß 2012 Published by Elsevier Ireland Ltd. doi:10.1016/j.anl.2011.12.006
weeks. Persistent means that symptoms are present for more than 4 days a week and for more than 4 weeks. The AR severity is classifiable as ‘mild’ or ‘moderate–severe’ [1]. Mild denotes that none of the following items are present: sleep disturbance, impairment of daily activities, leisure and/or sports, impairment of school or work, and other troublesome symptoms. Moderate– severe means that one or more of the items described above are present. Seasonal allergic rhinitis (SAR) caused by Japanese cedar pollen (Cryptomeria japonica; SAR-JCP) is the most common allergic disease in Japan. According to a national survey, the prevalence of rhinitis in Japan was 16% of Japanese population in 1992 and 21% in 2002 [2]. A recent study showed that over 35% of the Japanese population aged 20–50 suffers from SAR-JCP during JCP dispersal seasons [3]. JCP dispersal starts in early February, reaches a peak in
S. Fujieda et al. / Auris Nasus Larynx 39 (2012) 553–556
554 Table 1 Grading of allergy test. Grading
+++
++
+
Skin test
Erythema:41 mm Wheal: 16 mm 3 symptomsa + Sneezing 6 times Many
40–20 mm 15–10 mm 3 symptoms +
40–20 mm <10 mm 2 symptoms +
Intermediate of +++ and +
Noticeable at low magnification
Nasal provocation test Eosinophils in nasal smear a
1 symptom +
<20 mm <10 mm 0 0
Three symptoms are sneezing, rhinorrhea and nasal congestion.
March, and finishes in early April. Consequently, SAR-JCP patients endure allergic symptoms for at least 6–7 weeks, suggesting that SAR-JCP is classified as persistent AR by the ARIA criteria. Exposure of JCP is expected to induce one or more of the items (sleep disturbance, impairment of daily activities, leisure and/or sports, impairment of school or work, troublesome symptom) in SAR-JCP patients. The amount of JCP dispersal is larger than the level of pollen dispersal in the United States and Europe (ragweed, grass, birch, etc.) [4]. Consequently, all JCP patients are classified as moderate–severe. Half of patients with SAR-JCP are also allergic to mite/house dust [3]. The symptoms in JCP dispersal are absolutely more severe than those out of the JCP season in those patients [4]. These results lead many Japanese otorhinolaryngologists and allergists to believe that ARIA is an incongruous classification for SAR-JCP. Consequently, AR has been classified as seasonal AR (often caused by pollen, SAR) or perennial AR (caused by house dust or mites, PAR) in Japan [4,5]. In this review, we present a standard examination for diagnosis of AR and optimal classification for AR in Japan as a Japanese guideline [5]. 2. Examination for AR The first examination for AR is performed to determine whether the rhinitis is allergic or non-allergic in nature. Medical interviews are important. Rhinoscopy, nasal/sinus radiography, and determination of eosinophil counts in blood/nasal discharge are performed. The results are especially helpful in determining whether further and more detailed allergy examinations must be performed for patients. Sinusitis in residents of Western countries differs from sinusitis in Japanese patients with respect to the main infiltrating cells in nasal mucosa. The infiltrating cells comprise mainly eosinophils among westerners, while neutrophilic infiltration is predominant in Japanese people; ethnic differences of the Th1/ Th2/Th17 pattern are also apparent [6]. Therefore, the presence of eosinophils in nasal smear is an important diagnostic criterion for AR in Japan (Table 1). The second examination for AR is performed to identify antigens that cause rhinitis. Skin tests by antigen, determination of antigenspecific IgE titer (AS-IgE) in serum, and nasal provocation tests (NPT) are performed. Results of skin tests are obtainable rapidly and can be confirmed by patients themselves (Table 1). However, they present drawbacks including pain during skin puncture, possibility of development of allergic symptoms attributable to suspension of drug treatment for at least 1 week before testing. Scratch (prick) tests have not been used often in Japan. NPT are helpful for confirming allergens, and for evaluating the drug therapy effectiveness [5,7]. NPT are typically performed as follows: control paper disks are placed on the anterior end of the inferior nasal turbinate in both nostrils to confirm the absence of non-specific reactions. Paper disks containing allergens are placed at the same points, and the severity of rhinitis is evaluated based on the number of sneezes during the 5-minute period following placement of antigen disks, volume of nasal discharge, and severity of swelling of nasal mucosa using the scale presented in Table 1.
However, the drawbacks of this test include the limited availability of antigen disks (available for house dust and ragweed only). Quantification of AS-IgE can compensate for the drawbacks of skin reaction testing, and might be ordered at a central laboratory or commercial laboratories after blood sampling. This is the major method used to select the antigen in Japan. 3. Diagnosis Differentiation between AR and rhinitis because of causes other than allergy must be made during the first step of diagnosis. Diagnosis of AR and determination of allergens can be performed accurately when the patient has three major symptoms and exhibits eosinophils in nasal discharge, a positive skin test, and high AS-IgE. A positive result of NPT is positive proof of AR. The following should be considered when making a diagnosis of AR. First, AR can be diagnosed accurately when symptomatic patients have positive results for at least two of three testing items: eosinophils in nasal discharge, skin tests (or AS-IgE), and NPT. However, medical interview and skin tests or AS-IgE are important for the diagnosis of SAR outside of pollen season. Second, even when only one of the three tests (skin test, AS-IgE, NPT) produces a positive result, an AR diagnosis can be made when the patient has symptoms that are typical of it and exhibits moderate or severe reaction on allergy tests. This inference is particularly valid for patients for whom NPT cannot be performed. However, in patients with eosinophils in nasal discharge without positive results on other tests, allergic and non-allergic rhinitis must be differentiated carefully. Third, the results of skin tests and AS-IgE might be inconsistent. When the result of one test is not consistent with findings of a medical interview, both tests might be necessary. Fourth, patients with SAR have normal nasal mucosa and the absence of eosinophils in nasal discharge outside of pollen season. Fifth, vasomotor rhinitis and eosinophilic rhinitis are noninflammatory conditions with symptoms resembling those of AR and which are associated with nonspecific hypersensitivity without evidence suggestive of allergic disease. The symptoms of vasomotor rhinitis and eosinophilic rhinitis closely resemble those of AR, but these diseases are adult-onset in nature, and are associated with negative results of allergy tests [8]. However, patients with vasomotor/eosinophilic rhinitis respond well to drugs that are effective in treating patients with AR. 4. Classification of AR Purposes of classification are (1) evaluation of severity of AR, (2) evaluation of treatment efficacy and clinical course of individual patients or patient groups, and (3) evaluation of drug efficacy. Evaluation should be performed principally for symptoms, using objective findings for reference. Efforts must be undertaken to establish a method of evaluating patients based on both symptoms and objective findings. AR is classified as SAR or PAR. Nasal symptoms should be classified as sneezing/nasal discharge type, nasal obstruction type, or complete type based on the severity of the respective symptoms.
S. Fujieda et al. / Auris Nasus Larynx 39 (2012) 553–556
555
Table 2 Grading score of nasal symptom in allergic rhinitis. Grading score
4
3
2
1
0
Sneezing (number/day) Rhinorrhea (number/day) Nasal obstruction
21 times 21 times It is completely blocked all day long. It is not possible to do them at all.
10–6 times 10–6 times Symptoms are severe, with some mouth breathing during the day. Intermediate of 3 and 1
5–1 times 5–1 times No mouth breathing is done at all, but nasal obstruction occurs. It is all right.
0 0 None
Degree of disturbance of daily activitiesa
20–11 times 20–11 times Symptom is very severe, with much mouth breathing during the day. It is painful to do them
a
None
Daily activities include work, study, housekeeping, sleep, and going out.
Table 3 Classification of total nasal severity for allergic rhinitis. Status of sneezing or rhinorrhea (grade)a 4 Nasal obstruction (grade)
a
4 3 2 1 0
Very Very Very Very Very
severe severe severe severe severe
3
2
1
0
Very severe Severe Severe Severe Severe
Very severe Severe Moderate Moderate Moderate
Very severe Severe Moderate Mild Mild
Very severe Severe Moderate Mild No symptom
High grading scores are selected from sneezing or rhinorrhea.
Severity of AR should be determined based on the severity of each symptom, results of examination, and the degree of local change observed on gross inspection, among other factors. The principal nasal symptoms requiring assessment are sneezing, rhinorrhea, and nasal congestion. Symptom scores should be graded as 0–4. Grading of sneezing, rhinorrhea, and nasal congestion are evaluated based on the frequency of sneezing (number/day), frequency of nasal blowing (number/day), and duration of mouth-breathing, respectively (Table 2) [9]. Scoring should be performed for patients who can maintain an allergy diary. The total nasal symptom score should be calculated using the sum of grading. Total nasal severity of AR is evaluated by a grading score of nasal obstruction. That of sneezing/rhinorrhea and should be rated as ‘‘very severe’’, ‘‘severe’’, ‘‘moderate’’ and ‘‘mild’’ symptoms (Table 3) [9]. Visual inspection for local findings should be performed using rhinoscopy. PAR is characterized by pale nasal mucosa, watery nasal discharge, an increase in eosinophils in nasal discharge, and positive results of NPT. Red nasal mucosa suggests the presence of acute inflammation and/or acute allergy (such as reactions to pollen in patients with SAR during the pollen season). The presence of purulent nasal discharge suggests infection. 5. Medication score When patients with AR took medicine for allergic symptoms, the name of the medicine and times to be administered were recorded daily. The scores should be provided daily for each drug. When more than one drug is used, the total score is calculated for Table 4 Scoring system for subject medication score. Medicine
Score
Oral antihistamine or the leukotriene receptor antagonist Corticosteroids in nasal sprays Vasoconstrictors in nasal drops Antihistamine and releasers in eye drops Corticosteroid eye-drops Pre-maintenance dose of allergen-specific immunotherapy Maintenance dose of allergen-specific immunotherapy CelestamineR (Betamethasone and D-chlorpheniramine maleate)
1 2 1 1 2 0.5 1 2.5
the drugs used. The usual daily dose is considered the standard. Scores for oral corticosteroids must be obtained by calculating a prednisolone-equivalent anti-inflammatory dose (prednisolone 1 mg = 1 point). Other types of drugs should be scored appropriately according to Table 4 [10]. The symptom–medication score is calculated using the sum of the symptom and medication scores. Recent clinical studies require the symptom–medication score to evaluate the effect of treatment for AR. 6. QOL score AR is a chronic disease that is difficult to cure, although its symptoms can be controlled. The target of treatment of AR therefore tends to be considered improvement of quality of life (QOL). The World Health Organization (WHO) defines QOL as ‘‘Individuals’ perception of their position in life in the context of the culture and value systems in which they live and in relation to their goals, expectations, standards and concerns’’. Because perceptions of QOL might differ considerably among ethnic groups, cultures, and living environments, report forms should be prepared in consideration of the characteristics of the target population when evaluating patient QOL. The Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) has been used as an evaluation form specifically for patients with AR [11]. Because an evaluation form that is suitable for the Japanese population has been required, the Japanese RQLQ was prepared in 2002 by Okuda and the Committee for Preparation of QOL Evaluation Form for Patients with AR [4,12]. In addition to the classification of severity according to AR symptoms, the evaluation form must include a rating of QOL that includes individual perceptions of the disease. When using QOL as a factor in efficacy evaluation, the form should include evaluation by patients of attending physicians as a measure of the health care quality. A standardized form for evaluation of patient satisfaction must therefore be developed. 7. Criteria for determining prognosis Determination of short-term and long-term prognoses of patients receiving drug therapy requires observation, respectively, for at least 1–4 weeks and 1–3 months. Effective evaluation might also be performed by comparing the decrease in the symptom
556
S. Fujieda et al. / Auris Nasus Larynx 39 (2012) 553–556
scores and QOL scores between patient groups with different treatments (e.g., drug vs. placebo). Conflict of interest S. Fujieda is consultants and speaker of Kyorin, speaker of Sanofi Aventis, Ono and Kyowa Kirin, and has received grant/research support from Ono, MSD and GSK. K. Okubo is consultants of Kyorin, speaker of Taiho, Ono, Kyowa Kirin, Zeria and MSD. T. Enomoto is speaker of Kyowa Kirin. H. Kawauchi has received grant/research support from MSD and GSK. K. Masuyama is consultants of Kyorin, speaker of GSK, and has received grant/research support from MSD and GSK. H. Suzaki has received grant/research support from MSD and GSK. M. Okamoto consultants and speaker of Kyorin, speaker of Kyowa Kirin, Ono, Shionogi, MSD, Torii and GSK, has received grant/research support from MSD, GSK and Boehringer Ingelheim. H. Takenaka is speaker of GSK. References [1] Bousquet J, van Cauwenberge P, Khaltaev N. Allergic rhinitis and its impact on asthma. J Allergy Clin Immunol 2001;108:S147–334. [2] Nishima S, Chisaka H, Fujiwara T, Hayashi S, Hiraba K, Hisada N, et al. Surveys on the prevalence of pediatric bronchial asthma in Japan: a comparison
[3]
[4]
[5] [6]
[7]
[8] [9] [10]
[11]
[12]
between the 1982, 1992, and 2002 surveys conducted in the same region using the same methodology. Allergol Int 2008;58:37–53. Sakashita M, Hirota T, Harada M, Nakamichi R, Tsunoda T, Osawa Y, et al. Prevalence of allergic rhinitis and sensitization to common aeroallergens in a Japanese population. Int Arch Allergy Immunol 2009;151:255–61. Okamoto Y, Horiguchi S, Yamamoto H, Yonekura S, Hanazawa T. Present situation of cedar pollinosis in Japan and its immune responses. Allergol Int 2009;58:155–62. Okubo K, Kurono Y, Fujieda S, Ogino S, Uchio E, Odajima H, et al. Japanese guideline for allergic rhinitis. Allergol Int 2011;60:171–89. Zhang N, Van Zele T, Perez-Novo C, Van Bruaene N, Holtappels G, DeRuyck N, et al. Different types of T-effector cells orchestrate mucosal inflammation in chronic sinus disease. J Allergy Clin Immunol 2008;122:961–8. Kim YH, Jang TY. Proposed diagnostic standard using visual analogue scale and acoustic rhinometry in nasal provocation test in allergic patients. Auris Nasus Larynx 2011;38:340–6. Pattanaik D, Lieberman P. Vasomotor rhinitis. Curr Allergy Asthma Rep 2010; 10:84–91. Okuda M. Classification of severity of nasal symptom in allergic rhinitis. Otolaryngol Tokyo 1983;55:939–45. Segawa S, Takata Y, Wakita Y, Kaneko T, Kaneda H, Watari J, et al. Clinical effects of a hop water extract on Japanese cedar pollinosis during the pollen season: a double-blind, placebo-controlled trial. Biosci Biotechnol Biochem 2007;71:1955–62. Juniper EF, Thompson AK, Ferrie PJ, Roberts JN. Validation of the standardized version of the Rhinoconjunctivitis Quality of Life Questionnaire. J Allergy Clin Immunol 1999;104:364–9. Okuda M, Ohkubo K, Goto M, Okamoto H, Konno A, Baba K, et al. comparative study of two Japanese rhinoconjunctivitis quality-of-life questionnaires. Acta Otolaryngol 2005;125:736–44.
Contents lists available at SciVerse ScienceDirect
Auris Nasus Larynx journal homepage: www.elsevier.com/locate/anl
Examination, diagnosis and classification for Japanese allergic rhinitis: Japanese guideline Shigeharu Fujieda a,*, Yuichi Kurono b, Kimihiro Okubo c, Keiichi Ichimura d, Tadao Enomoto e, Hideyuki Kawauchi f, Keisuke Masuyama g, Minoru Goto c, Harumi Suzaki h, Yoshitaka Okamoto i, Hiroshi Takenaka j a
Department of Otolaryngology – Head & Neck Surgery, University of Fukui, Fukui, 23-11 Shimoaizuki, Eiheiji-Matsuoka-cho, Yoshida-gun, Fukui 910-1193, Japan Department of Otolaryngology – Head & Neck Surgery, Kagoshima University, 8-35-1 Sakuragaoka, Kagoshima 890-8520, Japan c Department of Otorhinolaryngology, Nippon Medical School, 1-1-5 Sendagi, Bunkyo-ku, Tokyo 113-8603, Japan d Department of Otolaryngology – Head & Neck Surgery, Jichi Medical University School of Medicine, 3311-1 Yakushiji, Shimotsuke, Tochigi 329-0498, Japan e NPO Japan Health Promotion Supporting Network, 3-68 Komatsubaradori, Wakayana, Wakayana 640-8269, Japan f Department of Otorhinolaryngology, Shimane University, 89-1 Enya-cho, Izumo, Shimane 693-8501, Japan g Department of Otorhinolaryngology, University of Yamanashi, 1110 Shimokato, Chuo, Yamanashi 409-3898, Japan h Department of Otorhinolaryngology, Showa University, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo 142-8666, Japan i Department of Otolaryngology, Head and Neck Surgery, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8670, Japan j Department of Otorhinolaryngology, Osaka Medical College, 2-7 Daigaku-cho, Takatsuki City, Osaka 569-8686, Japan b
A R T I C L E I N F O
A B S T R A C T
Article history: Received 30 August 2011 Accepted 13 January 2012 Available online 7 March 2012
Many countries throughout the world have experienced an increase in the prevalence of allergic rhinitis (AR), which has come to be a major cause of morbidity in developed countries. The pathology underlying AR is regarded as IgE-mediated type I allergy characterized by mucosal inflammation that occurs in response to allergen exposure. In Japan, AR caused by Japanese cedar pollen, the most common allergic disease, has become a salient public health challenge. Almost all primary care physicians and otorhinolaryngologists have been consulted by AR patients between February and April. Although most such patients have received treatment, numerous patients with AR have not received proper examinations for AR. Clinical guidelines are systematically developed statements that are designed to help practitioners make decisions about appropriate and effective health care. Guidelines in many countries including Japan have been published for AR. Unfortunately, those guidelines have remained untested. Moreover, they might be difficult for non-specialists to use. In this review, we specifically examine the present standard examination for diagnosis of AR and optimal classification for AR in Japan. We hope that this review would be used not only for the support of daily practice but also for selection of AR patients for clinical trials. ß 2012 Published by Elsevier Ireland Ltd.
Keywords: Japanese cedar pollen Guideline Perennial allergic rhinitis Seasonal allergic rhinitis
1. Introduction Allergic rhinitis (AR) is a type I allergic disease on nasal membranes. In principle, it is associated with sneezing, rhinorrhea, and nasal congestion as its major three symptoms. Allergic rhinitis and its Impact on Asthma (ARIA) recommended that AR is divided into ‘intermittent’ or ‘persistent’ [1]. Intermittent signifies that the symptoms are present for less than 4 days a week or for less than 4
* Corresponding author at: Division of Otorhinolaryngology – Head & Neck Surgery, Department of Sensory and Locomotor Medicine, Faculty of Medical Science, University of Fukui, Shimoaizuki, Matsuoka, Eiheiji-cho, Yoshida-gun, Fukui 910-1193, Japan. Tel.: +81 776 61 8407; fax: +81 776 61 8118. E-mail address: [email protected] (S. Fujieda). 0385-8146/$ – see front matter ß 2012 Published by Elsevier Ireland Ltd. doi:10.1016/j.anl.2011.12.006
weeks. Persistent means that symptoms are present for more than 4 days a week and for more than 4 weeks. The AR severity is classifiable as ‘mild’ or ‘moderate–severe’ [1]. Mild denotes that none of the following items are present: sleep disturbance, impairment of daily activities, leisure and/or sports, impairment of school or work, and other troublesome symptoms. Moderate– severe means that one or more of the items described above are present. Seasonal allergic rhinitis (SAR) caused by Japanese cedar pollen (Cryptomeria japonica; SAR-JCP) is the most common allergic disease in Japan. According to a national survey, the prevalence of rhinitis in Japan was 16% of Japanese population in 1992 and 21% in 2002 [2]. A recent study showed that over 35% of the Japanese population aged 20–50 suffers from SAR-JCP during JCP dispersal seasons [3]. JCP dispersal starts in early February, reaches a peak in
S. Fujieda et al. / Auris Nasus Larynx 39 (2012) 553–556
554 Table 1 Grading of allergy test. Grading
+++
++
+
Skin test
Erythema:41 mm Wheal: 16 mm 3 symptomsa + Sneezing 6 times Many
40–20 mm 15–10 mm 3 symptoms +
40–20 mm <10 mm 2 symptoms +
Intermediate of +++ and +
Noticeable at low magnification
Nasal provocation test Eosinophils in nasal smear a
1 symptom +
<20 mm <10 mm 0 0
Three symptoms are sneezing, rhinorrhea and nasal congestion.
March, and finishes in early April. Consequently, SAR-JCP patients endure allergic symptoms for at least 6–7 weeks, suggesting that SAR-JCP is classified as persistent AR by the ARIA criteria. Exposure of JCP is expected to induce one or more of the items (sleep disturbance, impairment of daily activities, leisure and/or sports, impairment of school or work, troublesome symptom) in SAR-JCP patients. The amount of JCP dispersal is larger than the level of pollen dispersal in the United States and Europe (ragweed, grass, birch, etc.) [4]. Consequently, all JCP patients are classified as moderate–severe. Half of patients with SAR-JCP are also allergic to mite/house dust [3]. The symptoms in JCP dispersal are absolutely more severe than those out of the JCP season in those patients [4]. These results lead many Japanese otorhinolaryngologists and allergists to believe that ARIA is an incongruous classification for SAR-JCP. Consequently, AR has been classified as seasonal AR (often caused by pollen, SAR) or perennial AR (caused by house dust or mites, PAR) in Japan [4,5]. In this review, we present a standard examination for diagnosis of AR and optimal classification for AR in Japan as a Japanese guideline [5]. 2. Examination for AR The first examination for AR is performed to determine whether the rhinitis is allergic or non-allergic in nature. Medical interviews are important. Rhinoscopy, nasal/sinus radiography, and determination of eosinophil counts in blood/nasal discharge are performed. The results are especially helpful in determining whether further and more detailed allergy examinations must be performed for patients. Sinusitis in residents of Western countries differs from sinusitis in Japanese patients with respect to the main infiltrating cells in nasal mucosa. The infiltrating cells comprise mainly eosinophils among westerners, while neutrophilic infiltration is predominant in Japanese people; ethnic differences of the Th1/ Th2/Th17 pattern are also apparent [6]. Therefore, the presence of eosinophils in nasal smear is an important diagnostic criterion for AR in Japan (Table 1). The second examination for AR is performed to identify antigens that cause rhinitis. Skin tests by antigen, determination of antigenspecific IgE titer (AS-IgE) in serum, and nasal provocation tests (NPT) are performed. Results of skin tests are obtainable rapidly and can be confirmed by patients themselves (Table 1). However, they present drawbacks including pain during skin puncture, possibility of development of allergic symptoms attributable to suspension of drug treatment for at least 1 week before testing. Scratch (prick) tests have not been used often in Japan. NPT are helpful for confirming allergens, and for evaluating the drug therapy effectiveness [5,7]. NPT are typically performed as follows: control paper disks are placed on the anterior end of the inferior nasal turbinate in both nostrils to confirm the absence of non-specific reactions. Paper disks containing allergens are placed at the same points, and the severity of rhinitis is evaluated based on the number of sneezes during the 5-minute period following placement of antigen disks, volume of nasal discharge, and severity of swelling of nasal mucosa using the scale presented in Table 1.
However, the drawbacks of this test include the limited availability of antigen disks (available for house dust and ragweed only). Quantification of AS-IgE can compensate for the drawbacks of skin reaction testing, and might be ordered at a central laboratory or commercial laboratories after blood sampling. This is the major method used to select the antigen in Japan. 3. Diagnosis Differentiation between AR and rhinitis because of causes other than allergy must be made during the first step of diagnosis. Diagnosis of AR and determination of allergens can be performed accurately when the patient has three major symptoms and exhibits eosinophils in nasal discharge, a positive skin test, and high AS-IgE. A positive result of NPT is positive proof of AR. The following should be considered when making a diagnosis of AR. First, AR can be diagnosed accurately when symptomatic patients have positive results for at least two of three testing items: eosinophils in nasal discharge, skin tests (or AS-IgE), and NPT. However, medical interview and skin tests or AS-IgE are important for the diagnosis of SAR outside of pollen season. Second, even when only one of the three tests (skin test, AS-IgE, NPT) produces a positive result, an AR diagnosis can be made when the patient has symptoms that are typical of it and exhibits moderate or severe reaction on allergy tests. This inference is particularly valid for patients for whom NPT cannot be performed. However, in patients with eosinophils in nasal discharge without positive results on other tests, allergic and non-allergic rhinitis must be differentiated carefully. Third, the results of skin tests and AS-IgE might be inconsistent. When the result of one test is not consistent with findings of a medical interview, both tests might be necessary. Fourth, patients with SAR have normal nasal mucosa and the absence of eosinophils in nasal discharge outside of pollen season. Fifth, vasomotor rhinitis and eosinophilic rhinitis are noninflammatory conditions with symptoms resembling those of AR and which are associated with nonspecific hypersensitivity without evidence suggestive of allergic disease. The symptoms of vasomotor rhinitis and eosinophilic rhinitis closely resemble those of AR, but these diseases are adult-onset in nature, and are associated with negative results of allergy tests [8]. However, patients with vasomotor/eosinophilic rhinitis respond well to drugs that are effective in treating patients with AR. 4. Classification of AR Purposes of classification are (1) evaluation of severity of AR, (2) evaluation of treatment efficacy and clinical course of individual patients or patient groups, and (3) evaluation of drug efficacy. Evaluation should be performed principally for symptoms, using objective findings for reference. Efforts must be undertaken to establish a method of evaluating patients based on both symptoms and objective findings. AR is classified as SAR or PAR. Nasal symptoms should be classified as sneezing/nasal discharge type, nasal obstruction type, or complete type based on the severity of the respective symptoms.
S. Fujieda et al. / Auris Nasus Larynx 39 (2012) 553–556
555
Table 2 Grading score of nasal symptom in allergic rhinitis. Grading score
4
3
2
1
0
Sneezing (number/day) Rhinorrhea (number/day) Nasal obstruction
21 times 21 times It is completely blocked all day long. It is not possible to do them at all.
10–6 times 10–6 times Symptoms are severe, with some mouth breathing during the day. Intermediate of 3 and 1
5–1 times 5–1 times No mouth breathing is done at all, but nasal obstruction occurs. It is all right.
0 0 None
Degree of disturbance of daily activitiesa
20–11 times 20–11 times Symptom is very severe, with much mouth breathing during the day. It is painful to do them
a
None
Daily activities include work, study, housekeeping, sleep, and going out.
Table 3 Classification of total nasal severity for allergic rhinitis. Status of sneezing or rhinorrhea (grade)a 4 Nasal obstruction (grade)
a
4 3 2 1 0
Very Very Very Very Very
severe severe severe severe severe
3
2
1
0
Very severe Severe Severe Severe Severe
Very severe Severe Moderate Moderate Moderate
Very severe Severe Moderate Mild Mild
Very severe Severe Moderate Mild No symptom
High grading scores are selected from sneezing or rhinorrhea.
Severity of AR should be determined based on the severity of each symptom, results of examination, and the degree of local change observed on gross inspection, among other factors. The principal nasal symptoms requiring assessment are sneezing, rhinorrhea, and nasal congestion. Symptom scores should be graded as 0–4. Grading of sneezing, rhinorrhea, and nasal congestion are evaluated based on the frequency of sneezing (number/day), frequency of nasal blowing (number/day), and duration of mouth-breathing, respectively (Table 2) [9]. Scoring should be performed for patients who can maintain an allergy diary. The total nasal symptom score should be calculated using the sum of grading. Total nasal severity of AR is evaluated by a grading score of nasal obstruction. That of sneezing/rhinorrhea and should be rated as ‘‘very severe’’, ‘‘severe’’, ‘‘moderate’’ and ‘‘mild’’ symptoms (Table 3) [9]. Visual inspection for local findings should be performed using rhinoscopy. PAR is characterized by pale nasal mucosa, watery nasal discharge, an increase in eosinophils in nasal discharge, and positive results of NPT. Red nasal mucosa suggests the presence of acute inflammation and/or acute allergy (such as reactions to pollen in patients with SAR during the pollen season). The presence of purulent nasal discharge suggests infection. 5. Medication score When patients with AR took medicine for allergic symptoms, the name of the medicine and times to be administered were recorded daily. The scores should be provided daily for each drug. When more than one drug is used, the total score is calculated for Table 4 Scoring system for subject medication score. Medicine
Score
Oral antihistamine or the leukotriene receptor antagonist Corticosteroids in nasal sprays Vasoconstrictors in nasal drops Antihistamine and releasers in eye drops Corticosteroid eye-drops Pre-maintenance dose of allergen-specific immunotherapy Maintenance dose of allergen-specific immunotherapy CelestamineR (Betamethasone and D-chlorpheniramine maleate)
1 2 1 1 2 0.5 1 2.5
the drugs used. The usual daily dose is considered the standard. Scores for oral corticosteroids must be obtained by calculating a prednisolone-equivalent anti-inflammatory dose (prednisolone 1 mg = 1 point). Other types of drugs should be scored appropriately according to Table 4 [10]. The symptom–medication score is calculated using the sum of the symptom and medication scores. Recent clinical studies require the symptom–medication score to evaluate the effect of treatment for AR. 6. QOL score AR is a chronic disease that is difficult to cure, although its symptoms can be controlled. The target of treatment of AR therefore tends to be considered improvement of quality of life (QOL). The World Health Organization (WHO) defines QOL as ‘‘Individuals’ perception of their position in life in the context of the culture and value systems in which they live and in relation to their goals, expectations, standards and concerns’’. Because perceptions of QOL might differ considerably among ethnic groups, cultures, and living environments, report forms should be prepared in consideration of the characteristics of the target population when evaluating patient QOL. The Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) has been used as an evaluation form specifically for patients with AR [11]. Because an evaluation form that is suitable for the Japanese population has been required, the Japanese RQLQ was prepared in 2002 by Okuda and the Committee for Preparation of QOL Evaluation Form for Patients with AR [4,12]. In addition to the classification of severity according to AR symptoms, the evaluation form must include a rating of QOL that includes individual perceptions of the disease. When using QOL as a factor in efficacy evaluation, the form should include evaluation by patients of attending physicians as a measure of the health care quality. A standardized form for evaluation of patient satisfaction must therefore be developed. 7. Criteria for determining prognosis Determination of short-term and long-term prognoses of patients receiving drug therapy requires observation, respectively, for at least 1–4 weeks and 1–3 months. Effective evaluation might also be performed by comparing the decrease in the symptom
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scores and QOL scores between patient groups with different treatments (e.g., drug vs. placebo). Conflict of interest S. Fujieda is consultants and speaker of Kyorin, speaker of Sanofi Aventis, Ono and Kyowa Kirin, and has received grant/research support from Ono, MSD and GSK. K. Okubo is consultants of Kyorin, speaker of Taiho, Ono, Kyowa Kirin, Zeria and MSD. T. Enomoto is speaker of Kyowa Kirin. H. Kawauchi has received grant/research support from MSD and GSK. K. Masuyama is consultants of Kyorin, speaker of GSK, and has received grant/research support from MSD and GSK. H. Suzaki has received grant/research support from MSD and GSK. M. Okamoto consultants and speaker of Kyorin, speaker of Kyowa Kirin, Ono, Shionogi, MSD, Torii and GSK, has received grant/research support from MSD, GSK and Boehringer Ingelheim. H. Takenaka is speaker of GSK. References [1] Bousquet J, van Cauwenberge P, Khaltaev N. Allergic rhinitis and its impact on asthma. J Allergy Clin Immunol 2001;108:S147–334. [2] Nishima S, Chisaka H, Fujiwara T, Hayashi S, Hiraba K, Hisada N, et al. Surveys on the prevalence of pediatric bronchial asthma in Japan: a comparison
[3]
[4]
[5] [6]
[7]
[8] [9] [10]
[11]
[12]
between the 1982, 1992, and 2002 surveys conducted in the same region using the same methodology. Allergol Int 2008;58:37–53. Sakashita M, Hirota T, Harada M, Nakamichi R, Tsunoda T, Osawa Y, et al. Prevalence of allergic rhinitis and sensitization to common aeroallergens in a Japanese population. Int Arch Allergy Immunol 2009;151:255–61. Okamoto Y, Horiguchi S, Yamamoto H, Yonekura S, Hanazawa T. Present situation of cedar pollinosis in Japan and its immune responses. Allergol Int 2009;58:155–62. Okubo K, Kurono Y, Fujieda S, Ogino S, Uchio E, Odajima H, et al. Japanese guideline for allergic rhinitis. Allergol Int 2011;60:171–89. Zhang N, Van Zele T, Perez-Novo C, Van Bruaene N, Holtappels G, DeRuyck N, et al. Different types of T-effector cells orchestrate mucosal inflammation in chronic sinus disease. J Allergy Clin Immunol 2008;122:961–8. Kim YH, Jang TY. Proposed diagnostic standard using visual analogue scale and acoustic rhinometry in nasal provocation test in allergic patients. Auris Nasus Larynx 2011;38:340–6. Pattanaik D, Lieberman P. Vasomotor rhinitis. Curr Allergy Asthma Rep 2010; 10:84–91. Okuda M. Classification of severity of nasal symptom in allergic rhinitis. Otolaryngol Tokyo 1983;55:939–45. Segawa S, Takata Y, Wakita Y, Kaneko T, Kaneda H, Watari J, et al. Clinical effects of a hop water extract on Japanese cedar pollinosis during the pollen season: a double-blind, placebo-controlled trial. Biosci Biotechnol Biochem 2007;71:1955–62. Juniper EF, Thompson AK, Ferrie PJ, Roberts JN. Validation of the standardized version of the Rhinoconjunctivitis Quality of Life Questionnaire. J Allergy Clin Immunol 1999;104:364–9. Okuda M, Ohkubo K, Goto M, Okamoto H, Konno A, Baba K, et al. comparative study of two Japanese rhinoconjunctivitis quality-of-life questionnaires. Acta Otolaryngol 2005;125:736–44.