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ORIGINAL
Short-term pre-operative systemic administration with
low-dose of steroid does not make a false-negative
diagnosis of definite eosinophilic chronic rhinosinusitis
after endoscopic sinus surgery
Chisa Fujimotoa,b, Koichi Tamurab, Shizuka Takaishib, Ikuji Kawataa, Yoshiaki Kitamurac, and Noriaki Takedac
Department of Otolaryngology, Yoshinogawa Medical Center, Tokushima, Japan
Department of Otolaryngology, Tokushima Municipal Hospital, Tokushima, Japanc
Department of Otolaryngology, Institute of Biomedical Sciences, The University of Tokushima Graduate School, Tokushima, Japanab

Abstract : According to JESREC criteria, definite eosinophilic chronic rhinosinusitis (ECRS) is postoperatively
diagnosed based on over 70 eosinophils in high power magnification fields of the resected nasal polyps in patients with probable ECRS. Preoperative systemic administration with steroid is a standard practice, because it
reduced intraoperative bleeding during endoscopic sinus surgery (ESS) in patients with ECRS. However, it wasrecently reported that systemic administration with steroid decreased the number of eosinophils in the nasal
polyps, leading to a false negative diagnosis of definite ECRS. To overcome the risk, we have adopted shortterm pre-operative systemic administration with low-dose of steroid and examined if our steroid administration
makes a false-negative diagnosis. We performed a retrospective chart review of 42 patients with probable ECRS.
Eleven patients were administered with 0.5 mg of bethametasone for 7 days before ESS, and other 31 patientswere not administered. The average number of eosinophils in nasal polyps in patients who were administeredwith steroid was 188 ± 167, which was not different from 199 ± 149 in the patients who were not administered.
These findings suggest that short-term preoperative administration with low-dose of steroid has few risk of a
false-negative diagnosis of definite ECRS. J. Med. Invest. 66 : 233-236, August, 2019
Keywords : eosinophilic chronic rhinosinusitis (ECRS), chronic rhinosinusitis with nasal polyps, preoperative systemic steroids,
endoscopic sinus surgery (ESS), Japanese Epidemiological Survey of Refractory Eosinophilic Chronic Rhinosinusitis (JESREC).

INTRODUCTION
Chronic rhinosinusitis (CRS) is a common otorhinolaryngological disease, and classified into CRS with or without nasal
polyps (1). In CRS with nasal polyps, eosinophil infiltration isdominant in Western countries (2). However, until the 1990s in
Japan and East Asia, neutrophil infiltration had been dominant
in CRS with nasal polyps, which was successfully treated withendoscopic sinus surgery (ESS) (3). Recently, the incidence of
CRS with nasal polyps with eosinophilic infiltration increased
gradually in Japan and East Asia (4,5). The CRS with nasal
polyps with eosinophilic infiltration is refractory, because nasal
polyps often recur soon after ESS (3). To differentiate from CRS
with nasal polyps of neutrophil infiltration, CRS with nasal
polyps of eosinophilic infiltration was denominated as eosinophilic CRS (ECRS) in Japan (6), and the JESREC (Japanese
Epidemiological Survey of Refractory Eosinophilic Chronic
Rhinosinusitis) Study has published the diagnostic criteria ofECRS (4). According to the criteria, probable ECRS is clinicallydiagnosed, and is classified into three severities : mild, moderateor severe. Definite ECRS is postoperatively diagnosed based on
the number of eosinophils in the resected nasal polyps.
Besides, intraoperative bleeding increases the risk of severe
Received for publication January 7, 2019 ; accepted February 18, 2019.
Address correspondence and reprint requests to Chisa Fujimoto, M.D.
Ph.D. Department of Otolaryngology, Yoshinogawa Medical Center,Tokushima, Japan. 120 Chiejima Aza Nishichiejima, Kamojima,
Yoshinogawa, Tokushima, Japan and Fax : +81-883-26-2300.

complications after ESS in patients with CRS. Perioperativemanagements such as the inverse Trendelenburg position,topical vasoconstrictor and controlled hypotension are usuallyused to reduce bleeding during ESS. Recently, it was reported
that preoperative systemic administration with steroid in thepatients with CRS with nasal polyps improved the visibility ofthe operative field with reduced bleeding during ESS (7) followed
by better surgical outcomes after ESS (8). Thus, in Japan preoperative systemic administration with steroid is now becoming astandard practice of otolaryngologist performing ESS for ECRS.
According to JESREC diagnostic criteria, definite ECRS
is diagnosed after ESS, based on the histological findings ofmore than 70 eosinophils in high power magnification fields ofthe resected nasal polyps. But, it was reported that systemicadministration with steroid decreased the number of eosinophils
in the nasal polyps in patients with CRS with nasal polyps (9).
Therefore, there is a risk that preoperative systemic administration with steroid makes a false negative diagnosis of definite
ECRS in patients with probable ECRS after ESS. To overcome
this problem, we have adopted to administer low dose of steroid
to patients with probable ECRS for short-term before ESS.
In the present study, an attempt was made to clarify if shortterm preoperative systemic administration with low-dose ofsteroid in patients with probable ECRS makes to a false-negative diagnosis of definite ECRS after ESS. For this purpose,
we examined the effects of oral administration with 0.5 mg/
day of bethametasone for 7 days before ESS on the number of
eosinophils in the resected nasal polyps of patients with probable
ECRS.

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C. Fujimoto, et al. Definite ECRS diagnosis with systemic steroid

PATIENTS AND METHODS
We performed a retrospective chart review of 92 patientswith CRS (60 males and 32 females ; 11 to 82 years old, average
age : 49.3 years old) who received ESS at Tokushima Municipal
Hospital, Tokushima, Japan from July 2013 to September 2015.
According to JESREC diagnostic criteria, probable ECRS andnon-ECRS were diagnosed in 42 and 50 patients respectively.
Eleven patients with probable ECRS were administered a daily
dose of 0.5 mg bethametasone tablet for 7 consecutive days andthe last one on the day before ESS, and another group of 31 patients received no preoperative pharmacological treatments. The
present study was approved by the Committee for Medical Ethicsof Tokushima Municipal Hospital.
Nasal polyps obtained during ESS were immediately fixed in
10% formalin, embedded in paraffin, and cut in thin sections of
2 µm. The sections were stained with hematoxylin-eosin, andthe number of eosinophils in nasal polyps was measured at highpower (×400) magnification fields in the densest area with cellular infiltrate beneath the epithelial surface.
Data were analyzed usingχ2 test, Student’s t-test, Mann-Whitney’s U test. P-value < 0.05 was considered statisticallysignificant.

RESULTS
According to JESREC diagnostic criteria of ECRS, probable
ECRS was diagnosed in 42 of 92 patients with CRS. Of the
42 patients with probable ECRS, 31 were males and 11 werefemales (15 to 77 years old, average age : 52.9 years old). Andamong the 50 patients with non-ECRS, 29 were males and 21
were females (11 to 82 years old, average age : 46.3 years old).
Probable ECRS were further subdivided into 3 groups as follows : 10 mild, 20 moderate and 12 severe. The prevalence of
probable ECRS increased with age and reached a maximum atthe sixth decade, and non-ECRS developed irrespective of age(Figure 1). Definite ECRS (25 males and 9 females ; 29 to 77years old, average age : 54.8 years old) was postoperatively diagnosed in 34 of the 42 patients with probable ECRS, based on thenumber of eosinophils in the resected nasal polyps according toJESREC diagnostic criteria.
Eleven of 42 patients with probable ECRS were administeredlow-dose of steroid orally for 7 days before ESS. No differences insex, age or severity were noted between patients with or without
preoperative treatment (Table 1). The number of eosinophils

Table 1 Characteristics of patients with probable ECRSSteroid(n = 11)

Non-steroids(n = 31)Male

1021Female

1

10

54.0 ± 17.1

52.5 ± 12.7

P-value

Sex

Age

0.13*
0.77**

Severity
Mild37Moderate

317Severe* :χ2 test

5** : Student’s t-test

0.49***

7*** : Mann–Whitney U test

was 188 ± 167 in high power magnification fields in the nasal
polyps of patients with short-term preoperative systemic administration of low-dose of steroid. The number of eosinophils in thenasal polyps of the remaining 31 patients who were received nopharmacological treatment was 199 ± 149 in high power magnification fields, which was not different from that with shortterm preoperative systemic administration with low-dose ofsteroid (Figure 2). In addition, among mild, moderate and severegroups, there were no differences of distribution of eosinophil
number in the nasal polyps between patients with or without
short-term preoperative administration with low-dose of steroid(Figure 3).

DISCUSSIONSIn the present study, according to JESREC diagnosis criteria,
about half of patients with CRS were given the diagnosis ofprobable ECRS, probably because of increasing incidence of CRS
with nasal polyposis that is infiltrated by eosinophils in Japanand East Asia (4,5). The prevalence of ECRS, but not non-ECRS

Figure 2 The number of eosinophils in the nasal polyps in patients
Figure 1 The prevalence of probable ECRS and non-ECRS at each
decade. ECRS : eosinophilic chronic rhinosinusitis.

with probable ECRS with or without PSS. Columns and bars represent average and standard deviation. ECRS : eosinophilic chronicrhinosinusitis. PSS : preoperative systemic steroid. HPF : high power
magnification fields.

The Journal of Medical Investigation Vol. 66 August 2019235

and/or submucosal turbinotomy, we cannot compare amountof intraoperative blood loss and surgical time with low dose ofsteroid to those without one.

CONCLUSION
In the present study, systemic administration with 0.5 mg ofbethametasone for 7 days did not decrease the number of eosinophils in the nasal polyps in patients with probable ECRS. Thus,
it is suggested that short-term preoperative administration with
low-dose of steroid has few risk of a false-negative diagnosis ofdefinite ECRS after ESS. However, a randomized prospective
controlled study should be undertaken to confirm our conclusion.
Furthermore, there is also a need to evaluate how short-term
preoperative administration with low-dose steroid reduces therisk of complication after ESS.

CONFLICT OF INTEREST
The authors declare no conflicts of interest.
Figure 3 The distribution of eosinophil number in the nasal polyps

in patients with mild, moderate and severe probable ECRS. Definite
ECRS is diagnosed in patients with probable ECRS when their nasal
polyps contain more than 70 eosinophils (dotted line) in high power
magnification field (HPF). ECRS : eosinophilic chronic rhinosinusitis.
Open circles : PSS. Closed circles : non-PSS. PSS : preoperative systemic steroid.

increased with age with the maximum prevalence at the sixth
decade. ECRS is often associated with asthma, probably becauseof the same underlying pathophysiology of eosinophilic inflammation of the respiratory tracts (4). Therefore, it is suggested theprevalence of ECRS is similar to that of asthma with the maximum prevalence at the early seventh decade (10).
It was reported that daily administration with prednisolone
at a dose of 15 mg for 10 days or 20 mg for 14 days reduced thenumber of eosinophils in the nasal polyps of patients with CRS
with nasal polyps (9,11). Accordingly, there was a possibility thatpreoperative administration with steroid reduced the numberof eosinophils in the nasal polyps, resulting in a false negative
diagnosis of definite ECRS after ESS, because definite ECRS
is diagnosed based on the microscopic findings of more than 70
eosinophils in high power magnification fields of the resectednasal polyps. But, the possibility is unlikely, because as shownin the present study, the number of eosinophils in the nasal polyps in patients with ECRS who received preoperative systemic
administration with 0.5 mg of betamethasone that is equivalent
to 5 mg of prednisone for 7 days was not different from thatwithout any preoperative pharmacological treatment. Moreover,three patients (2 of mild and 1 of moderate) may have been givena false negative diagnosis of definite ECRS. But, the risk is also
unlikely, because the distribution of eosinophil number in thenasal polyps after short-term preoperative systemic administration with low-dose of steroid was not different from that without
any preoperative pharmacological treatment among mild andmoderate groups. Taken together, these findings suggest thatshort-term preoperative systemic administration with low-doseof steroid did not make a false-negative diagnosis of definite
ECRS after ESS.
Limitations : The present study was a retrospective chart
review, but not randomized controlled one. Because individual
operative methods varied among ESS with/without septoplasty

ACKNOWLEDGEMENTS
We would like to acknowledge the support of Hiroshi Kiyoku
and colleagues of the Department of Pathology of Tokushima
Municipal Hospital.

REFERENCES
1.

2.

3.

4.

5.

6.

Fokkens WJ, Lund VJ, Mullol J, Bachert C, Alobid I,Baroody F, Cohen N, Cervin A, Douglas R, Gevaert P,Georgalas C, Goossens H, Harvey R, Hellings P, Hopkins C,
Jones N, Joos G, Kalogjera L, Kern B, Kowalski M, Price D,Riechelmann H, Schlosser R, Senior B, Thomas M, Toskala
E, Voegels R, Wang de Y, Wormald PJ : European Position
Paper on Rhinosinusitis and Nasal Polyps 2012. Rhinol 23
Suppl 3, 1-298, 2012.
Van Zele T, Claeys S, Gevaert P, Van Maele G, Holtappels G,
Van Cauwenberge P, Bachert C : Differentiation of chronicsinus diseases by measurement of inflammatory mediators.
Allergy 61 : 1280-1289, 2006
Nakayama T, Yoshikawa M, Asaka D, Okushi T, Matsuwaki
Y, Otori N, Hama T, Moriyama H : Mucosal eosinophilia
and recurrence of nasal polyps - new classification of chronicrhinosinusitis. Rhinology 49 : 392-396, 2011
Tokunaga T, Sakashita M, Haruna T, Asaka D, Takeno S,Ikeda H, Nakayama T, Seki N, Ito S, Murata J, Sakuma
Y, Yoshida N, Terada T, Morikura I, Sakaida H, Kondo K,Teraguchi K, Okano M, Otori N, Yoshikawa M, Hirakawa
K, Haruna S, Himi T, Ikeda K, Ishitoya J, Iino Y, Kawata R,Kawauchi H, Kobayashi M, Yamasoba T, Miwa T, Urashima
M, Tamari M, Noguchi E, Ninomiya T, Imoto Y, Morikawa
T, Tomita K, Takabayashi T, Fujieda S : Novel scoring system and algorithm for classifying chronic rhinosinusitis: theJESREC Study. Allergy 70 : 995-1003, 2015
Kim SJ, Lee KH, Kim SW, Cho JS, Park YK, ShinSY : Changes in histological features of nasal polyps in a
Korean population over a 17-year period. Otolaryngol HeadNeck Surg 149 : 431-437, 2013
Haruna S, Nakanishi M, Otori N, Moriyama H : Histopathological features of nasal polyps with asthma association : an immunohistochemical study. Am J Rhinol

236

7.

8.

C. Fujimoto, et al. Definite ECRS diagnosis with systemic steroid

18 : 165-172, 2004
Sieskiewicz A, Olszewska E, Rogowski M, Grycz E : Preoperative corticosteroid oral therapy and intraoperative bleeding during functional endoscopic sinus surgery in patientswith severe nasal polyposis : a preliminary investigation.
Ann Otol Rhinol Laryngol 115 : 490-494, 2006
Wright ED, Agrawal S : Impact of perioperative systemic
steroids on surgical outcomes in patients with chronicrhinosinusitis with polyposis : evaluation with the novel
Perioperative Sinus Endoscopy (POSE) scoring system.
Laryngoscope 117 : 1-28, 2007

9.

Hong SJ, Lee JK, Lee HS, Lee JY, Pyo JS, Lee KC : Availability of preoperative systemic steroids on endoscopic sinus
surgery for chronic rhinosinusitis with nasal polyposis.
Yonsei Med J 55 : 1683-1690, 2014
10. Ichinose M, Sugiura H, Nagase H, Yamaguchi M, Inoue H,
Sagara H, Tamaoki J, Tohda Y, Munakata M, Yamauchi K,
Ohta K : Japanese guidelines for adult asthma 2017. Allergol Int 66 : 163-189, 2017
11. Won TB, Jang E, Min SK, Kim SW : Treatment outcomesand predictors for systemic steroids in nasal polyposis. Acta
Otolaryngol 132 Suppl 1 : 82-87, 2012