Scholarly Journal of
Otolaryngology
DOI: 10.32474/SJO.2022.08.000286

Research Article

ISSN: 2641-1709

Epipharyngeal Abrasive Therapy for Patients with
Immunoglobulin A Nephropathy: A Retrospective Study
Manabu Mogitate*
Department of ENT, Mogitate ENT Clinic, Japan*Corresponding Author: Manabu Mogitate, Mogitate ENT Clinic, 1-2-5 Sekiguchi-Daiichi Building 401, Hisamoto, Takatsu-ku,
Kawasaki-City, Kanagawa-Prefecture 213-0011, Japan
Received:

May 16, 2022

Published:

May 27, 2022

Abstract
The incidence of chronic epipharyngitis is high among patients with immunoglobulin A nephropathy (IgAN). The current study
aimed to evaluate the efficacy of epipharyngeal abrasive therapy (EAT) for IgAN. This retrospective study assessed the medical
records of 21 patients with IgAN who visited my clinic between November 2016 and October 2017. All patients presented withchronic epipharyngitis and received EAT. In total, 19 participants who were treated until the final session were divided into group
A (n = 10, those who had combined EAT before and after tonsillectomy and steroid pulse therapy) and group B (n = 4, those whose
condition did not improve after tonsillectomy and pulse therapy and n = 2, those with hematuria recurrence after remission). Data
about the characteristics of patients and changes in creatinine (Cr) levels, estimated glomerular filtration rate (eGFR), urinary
protein levels, and urinary occult blood level before and after EAT were analyzed. There was no significant difference in terms of Cr
levels and eGFR before and after EAT. The urinary protein (p < 0.001) and occult blood (p = 0.003) levels significantly differed before
and after EAT. Moreover, the duration of urinary occult blood significantly decreased after EAT in group B (p = 0.047). Improvement
in hematuria was significantly faster in group B than in group A (p = 0.041). EAT for chronic epipharyngitis can improve hematuria
and can be used as additional treatment in patients with IgAN.
Keywords: Chronic epipharyngitis; epipharyngeal abrasive therapy; IgA nephropathy; nasopharynx

Introduction
Immunoglobulin A nephropathy (IgAN) is the most frequent
type of primary glomerulonephritis [1]. Moreover, it is currently
the second most frequent indication for dialysis after diabetic
nephropathy in Japan [2]. Approximately 30%–40% of patients with
IgAN who do not receive treatment develop end-stage renal failure[3]. Focal infections of the palatine tonsils are associated with IgAN
development, and bilateral palatine tonsillectomy is effective against
IgAN. Combined bilateral palatine tonsillectomy and steroid pulse
therapy has good clinical outcomes among patients with IgAN [4].
However, despite this treatment, some patients experience residual
or relapsing hematuria [5]. Patients with IgAN have a high incidenceof chronic epipharyngitis and tonsillitis [6]. Epipharyngeal abrasive
therapy (EAT) is effective against IgAN [7,8]. However, only a few
studies have reported this notion. Further, which patients should
undergo EAT remains unclear. Before EAT can be used as additional
treatment for patients with IgAN, its efficacy against IgAN must
be validated based on improvement in clinical findings (including
hematuria). My outpatient clinic specializes in the treatment of

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chronic epipharyngitis, and it has a higher number of patients
who receive therapy for chronic epipharyngitis than other local
clinics and hospitals [9]. About 20 patients with IgA nephropathy
chose and receive EAT annually. Acute epipharyngitis is a condition
characterized by colds, which is a type of viral infection. It is causedby different viruses, bacteria, and chemicals. Chronic epipharyngitis[10] is a persistent inflammation of the epipharynx, regardless ofthe cause, which causes different symptoms. Chronic epipharyngitis
can be classified as a direct symptom of epipharyngeal inflammation(such as chronic sore throat and throat discomfort), autonomic
symptom (including dizziness), or focal disease (such as IgAN andpalmoplantar pustulosis) [11].
EAT is a local treatment for chronic epipharyngitis, and it
has been used by Horiguchi since the 1960s. EAT has recently
been reported as one of the treatment options for patients
suffering from long coronavirus disease (COVID) [12,13]. Imai[14] reported that among the symptoms of long COVID, fatigue,headache, and attention disorder relieved by approximately 1874Sch J Oto

month of EAT. Hagino [15] also reported the effectiveness of EAT
on Postural Orthostatic Tachycardia Syndrome (POTS) associatedwith long COVID symptoms. In addition, Tanaka [16] reported theeffectiveness of intranasal sphenopalatine ganglion stimulation(INSPGS), a technique similar to EAT, in treating patients with long
COVID. Furthermore, Nishi [17] provided histological evidenceof EAT inducing squamous epithelialization of ciliated cells andinhibiting the expression of angiotensin-converting enzyme 2(ACE2) and transmembrane protease, serine 2 (TMPRSS2), thereby
preventing the entry of SARS-CoV-2 into the cells. They explained
the mechanism of action of EAT by referring to a report by Hotta[11]. The following three mechanisms of action of EAT wereexplained:a) anti-inflammatory (astringent and bactericidal) action ofzinc chloride,b)

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phlebotomy action, andc)vagus nerve stimulation action. In 2010, Hotta [18]showed that not only chronic tonsillitis but also chronic
epipharyngitis can be a focal infection for IgAN based on thesimilarity between tonsil and epipharyngeal cells.

Thereafter, EAT was commonly utilized by several
otolaryngologists in Japan. In a previous study, Tanaka [19], anotolaryngologist at a clinic, reported a patient treated with zincchloride abrasive therapy. Further, although tonsillectomy alone
was performed, the patient’s urinary findings normalized. Higa [20],an otolaryngologist at a university hospital, showed that EAT had atherapeutic effect in six patients with IgAN with residual hematuria
after tonsillectomies who were referred to an otolaryngologist by anephrologist.

However, in which patients should EAT be performed has
not been established yet. The current study investigated theeffectiveness of EAT among patients with IgAN who presented withchronic epipharyngitis. Moreover, to evaluate the effectiveness of
EAT, patients with IgAN who went to my clinic were further divided
into groups according to the treatment provided in the nephrology
department. If EAT was found to be effective against IgAN and theurinary findings improved, such treatment can be considered forpatients who have no other treatment options and who can only
undergo follow-up. Otolaryngologists can facilitate EAT in patientswith IgAN, instead of tonsillectomy, and their progress can bemonitored. The current study aimed to evaluate the effectivenessof EAT treatment on the blood and urinary findings of patients with
IgAN who visited my clinic.

Materials and Methods

Study design/Sample size
In this retrospective study, I evaluated the clinical data of 21
patients with IgAN who visited my clinic for the examination andtreatment of chronic epipharyngitis between November 2016 andOctober 2017. It was conducted in accordance with the Declarationof Helsinki. Since the ethics committee is not located in my clinic,
the research plan was submitted to the ethics committee of Ota
General Hospital (approval no. 19010). All patients provided
informed consent.

Setting/study population

At the initial visit, all patients underwent endoscopic
examination. Thereafter, 1% zinc chloride was applied to theepipharynx via the nasal insertion of a cotton swab and the oral
insertion of an applicator once per week for at least 12 weeks(Figure 1). The treatment of two patients was discontinued, and thecause was not identified. Therefore, the final analyses included thedata of 19 patients. All patients who were evaluated were included,
rather than randomly selected, in the analysis. Data about age, sex,
presence or absence of referral to my clinic from a nephrologist,
previous treatments, chief complaint, and urine occult blood levels
were extracted from the medical records. There was no change inurinary occult blood level if it remained at the pretreatment level of
3+. It improved if the level changed with at least one point (e.g., from3+ to 2+) and negative if the level became negative. If the urinary
occult blood level was worse after treatment, it was consideredworsening. The estimated glomerular filtration rate (eGFR) andurinary protein and urinary occult blood levels before and after
EAT were compared to determine changes in creatinine (Cr) levels
in 19 patients who were treated until the final session. Further,
the patients were divided into two groups—those who underwent
tonsillectomy and received steroid pulse therapy and those who
did not received treatments. Then, they were further classified
into groups A and B based on the timing of EAT initiation (Table
1). Group A comprised 10 patients with combined EAT before andafter tonsillectomy and steroid pulse therapy. Group B included
four patients who continually presented with hematuria after
tonsillectomy + pulse therapy and two patients with hematuria
recurrence after remission.

Table 1: Groups were further divided based on the timing of EAT initiation.

Group AGroup B
Others

Negative

Improved

Unchanged

Started EAT before or after tonsillectomy + pulse therapy

6

3

1

Remission was achieved with tonsillectomy + pulse therapy, but hematuria relapse subsequently occurred

2

Positive urinary occult blood test result after tonsillectomy + pulse therapy
Only preferred EAT (without tonsillectomy or pulse therapy)

1

1

Worsening

2
2

Citation: Manabu Mogitate*. Epipharyngeal Abrasive Therapy for Patients with Immunoglobulin A Nephropathy: A Retrospective Study.
Sch J Oto 8(3)-2022. SJO. MS.ID.000286. DOI: 10.32474/SJO.2022.08.000286.

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Figure 1: Electron endoscopic findings of the epipharynx.
a. White light image of the epipharynx.
b. Image obtained during epipharyngeal abrasion therapy (EAT).
c. Image obtained after EAT.
d. Schematic diagram of EAT (previously referred to as B spot therapy), which is a therapeutic strategy involving the applicationof a scrape with 1% zinc chloride to the epipharynx via the nasal insertion of a cotton swab and the oral insertion of an
applicator. The epipharynx of a patient with chronic epipharyngitis was normal on endoscopy; however, significant bleedingin painful areas occurred. Further, white light images were challenging to examine.

Data collection

Results

The blood and urine test whose data were used in this study
were performed by the nephrologist of the facilities where thepatients were being followed. The patients then brought theirresults to my clinic where I analyzed them. A total of 16 and 19
patients underwent blood and urine testing, respectively.

Table 2 shows the characteristics of patients. In total, 19 of 21
patients received treatments until the final session. Two patients
dropped out. However, the reasons were unknown. Data wereobtained from 16 cases for blood tests and 19 cases for urine tests.
The mean age of the patients was 27.8 (range: 16–64) years, and10 patients were men. All patients were followed-up until the
final treatment session. Results showed no statistically significant
differences in terms of Cr levels and eGFR before and after EAT(Figure 2). Moreover, based on the statistical analysis, the urinary
protein (p < 0.001) and urinary occult blood (p = 0.003) levels
significantly improved before and after EAT (Figure 3). The groups
were further divided based on the timing of EAT initiation. Table 2
shows the result of the urinary occult blood test. EAT significantly

Statistical analysis

Using the Kaplan–Meier method, the changes in urinary protein
and occult blood levels were analyzed, and the Wilcoxon signedrank test was utilized to assess changes in eGFR and Cr levels. Allanalyses were performed using the Statistical Package for the Social
Sciences for Windows version 22.0 (IBM Japan, Tokyo, Japan). A pvalue of <0.05 was considered statistically significant.

Citation: Manabu Mogitate*. Epipharyngeal Abrasive Therapy for Patients with Immunoglobulin A Nephropathy: A Retrospective Study.
Sch J Oto 8(3)-2022. SJO. MS.ID.000286. DOI: 10.32474/SJO.2022.08.000286.

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improved urinary occult blood levels in six patients in group B(6.00 ± 3.11) compared with group A (16.9 ± 2.40) (p = 0.047). Of
six patients in group B, four had urinary occult blood levels that
did not improve with tonsillectomy + pulse therapy. Two achieved
remissions with tonsillectomy + pulse therapy. However, they

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subsequently experienced hematuria relapse. The Cr and urinary
protein levels as well as eGFR did not improve after EAT in group
B (Figure 4). However, their urinary occult blood levels (p = 0.014)
significantly improved.

Figure 2: Analysis based on the Kaplan–Meier method of the negative urinary occult blood.
Group A: Ten patients received EAT before and after tonsillectomy + pulse therapy.
Group B: Six patients, including four patients with urinary occult blood levels that did not improve with tonsillectomy + pulse
therapy and two patients who achieved remission with tonsillectomy + pulse therapy but subsequently experienced hematuria
relapse.
EAT significantly reduced the duration of urinary occult blood reduction in group B.

Table 2: Characteristics of patients with immunoglobulin A nephropathy.
Age

16–64 years

Mean age: 37.8 years

Referral from a hospital nephrologist

Present: n = 8

Absent: n = 13

Sex

Treatment administered at nephrology clinics

Male: n = 10

Tonsillectomy + pulse therapy: n = 16

Female: n = 11

Tonsillectomy alone: n = 1
Pulse therapy alone: n = 1
None: n = 3

Citation: Manabu Mogitate*. Epipharyngeal Abrasive Therapy for Patients with Immunoglobulin A Nephropathy: A Retrospective Study.
Sch J Oto 8(3)-2022. SJO. MS.ID.000286. DOI: 10.32474/SJO.2022.08.000286.

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Figure 3: Changes in creatinine (Cr) levels, estimated glomerular filtration rate (eGFR), urinary protein levels, and urinary
occult blood levels before and after EAT.
Statistical analysis revealed no significant changes in creatinine (Cr) levels or estimated glomerular filtration rate (eGFR) before
and after EAT. The urinary protein and occult blood levels improved after EAT, with significant differences observed in 19
patients until the final sessions.

Citation: Manabu Mogitate*. Epipharyngeal Abrasive Therapy for Patients with Immunoglobulin A Nephropathy: A Retrospective Study.
Sch J Oto 8(3)-2022. SJO. MS.ID.000286. DOI: 10.32474/SJO.2022.08.000286.

878

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Volume 8 - Issue 3

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Figure 4: Changes in creatinine (Cr) levels, estimated glomerular filtration rate (eGFR), urinary protein levels, and urinary
occult blood levels before and after EAT.
Analysis of six patients (group B), including four whose urinary occult blood levels did not improve with tonsillectomy + pulse
therapy and two patients who achieved remission with tonsillectomy + pulse therapy but subsequently experienced hematuria
relapse, revealed that their Cr levels and eGFR did not improve after EAT. Analysis of group B revealed that the urinary
protein levels did not improve. However, their urinary occult blood levels were significantly better after EAT.

Discussion
In November 2016, my clinic developed a specialized outpatient
clinic for the diagnosis and treatment of chronic epipharyngitis [9].
Approximately 200 new patients are examined annually, which
included 21 with IgAN in the first year. The number of patients with
IgAN who chose EAT was higher at my institution than at other local
otolaryngological institutions. Therefore, physicians at my clinic
have real-world experience in investigating the efficacy of EAT
among patients with IgAN. However, to the best of my knowledge,
no study about the efficacy of EAT against IgAN has been publishedin the English literature by otolaryngologists. IgAN is most common
in the second to fifth decades of life. According to data from theJapan Renal Biopsy Registry, which was established by the JapaneseSociety of Nephrology in 2007, the mean ages of patients with IgAN
are 37.2 years in men and 35.7 years in women (n = 660) in Japan[21]. The incidence of IgAN does not differ between sexes among

Japanese patients 15. These findings are consistent with those ofthis study. Approximately 40% of patients were referred to my clinic
by hospital nephrologists in this study. Nephrologists commonlyrefer patients with IgAN to otolaryngologists for tonsillectomy. In
the future, physicians can make referrals for EAT.
More studies about chronic epipharyngitis are published, andboth patients with IgAN and physicians who treat them understandthe role of chronic epipharyngitis in IgAN. Several patients present
to otolaryngology clinics and choose EAT even without a referral.
Therefore, otolaryngologists in hospitals and clinics will manage
more patients requesting EAT in the future, and they should beaware of this treatment method. Approximately 80% of patientswith IgAN who visited my clinic for EAT were treated withtonsillectomy + steroid pulse therapy. This therapeutic technique
is one of the most common treatment options for IgAN in Japan.
The 2017 IgAN guidelines state that tonsillectomy + pulse therapy

Citation: Manabu Mogitate*. Epipharyngeal Abrasive Therapy for Patients with Immunoglobulin A Nephropathy: A Retrospective Study.
Sch J Oto 8(3)-2022. SJO. MS.ID.000286. DOI: 10.32474/SJO.2022.08.000286.

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can improve urinary findings in patients with IgAN and inhibits
the progression of renal dysfunction. Therefore, it should beconsidered as a treatment option [22]. If more data showing theefficacy of EAT are collected, it can be recommended to patientswith IgAN. All 21 patients who visited my clinic for EAT did notexhibit subjective otolaryngological symptoms. Patients withchronic epipharyngitis commonly have non-specific complaints
or localized throat discomfort or postnasal drip. Sugita reported
that several otolaryngologists overlook the presence of chronic
epipharyngitis even if patients complain of localized symptoms
in the epipharynx [23]. Furthermore, chronic epipharyngitis may
be missed after an endoscopic examination as the epipharynx iscommonly examined while in a chronic inflammatory state [23]. If
patients with IgAN visit an otolaryngologist, they do not complainof otolaryngological symptoms; therefore, the epipharynx should
be visualized and an abrasive examination of the epipharynx
should be performed if chronic epipharyngitis is suspected. EAT isthe diagnostic treatment for epipharyngitis, and examinations forbleeding can help diagnose chronic epipharyngitis.

In this study, 21 patients with IgAN who visited my clinicpresented with chronic epipharyngitis. The epipharynx is at theforefront of the nasopharynx-associated lymphoid tissues where
inhaled antigens from the nostrils are initially encountered.
Therefore, this area is physiologically mildly inflamed even among
healthy individuals. The exacerbation of glomerular vasculitis inpatients with IgAN is associated with inflammation of the acute
upper respiratory tract where epipharyngeal inflammation isinevitable and highly inflammatory [18]. After tonsillectomy,
patients with IgAN can present with gross hematuria associatedwith acute pharyngitis. Hotta showed that chronic epipharyngitis
caused by chronic irritation by antigens in the epipharynx may playa focal infectious role similar to that in chronic inflammation of thepalatine tonsils. Moreover, it may be involved in the immunologicaleffects of the epipharynx–kidney axis on the kidneys and thedevelopment of secondary diseases [24]. In this study, 9 of 19
patients who completed EAT had negative urinary occult blood test
result after treatment. A previous study [25] assessed 24 patients
who underwent EAT. Results showed that hematuria disappearedin 83% of patients. Among them, 19 continually experienced
hematuria after combined tonsillectomy and pulse therapy. In
addition, this study showed that patients with severe hematuria
were treated with additional steroid pulse therapy to reduce
inflammation. Moreover, patients with mild hematuria had a highrate of resolution after EAT alone [25]. Persistent urine occult bloodin patients with IgAN indicates residual focal inflammation causing
glomerular vasculitis. In this study, there was a difference in thetime wherein urinary occult blood disappeared between groups
A and B because the remaining inflammatory lesions were in theepipharynx and EAT was effective in reducing the volume of urinary
occult blood in these patients.
The absence of hematuria reflects the disappearance ofglomerular vasculitis, which contributes to a better long-term

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prognosis among patients with IgAN [26]. Thus, in this study,
urinary occult blood level was used to assess the therapeutic
efficacy of EAT against chronic epipharyngitis among patients with
IgAN. Further, hematuria is an important indicator for treatment
efficacy among patients with IgAN. In this study, the urinary occult
blood and protein levels significantly reduced among 19 patients
who underwent all EAT sessions. In group B, the Cr and protein
levels and eGFR did not improve with EAT. However, the urinary
occult blood levels were significantly better. Hence, EAT is effective
for urinary occult blood. In the current research, several patientswith IgAN had reduced urinary findings. Group A included patients
who just had tonsillectomy or who were on steroid pulse therapy.
In such a case, whether the improvement in urinary findings was
attributed to EAT alone could not be confirmed. By contrast, group
B included patients who had tonsillectomy + steroid pulse therapy,
which has been completed and has elapsed time, or those who
relapsed after a mild recovery based on urinary findings. Hence,
the assessment of group B may explain the efficacy of EAT alone.
Tonsillectomy + pulse therapy with EAT may be useful regardlessof the patient’s current treatment if it has some benefits among
patient with IgAN. If there is a need to limit patients, EAT is better
indicated for group B.
The current study included patients with IgAN who came to myclinic for EAT. Patients with IgAN who do not prefer EAT are basicallymonitored by nephrologists. It is ethically impossible to followup patients who come to my clinic for EAT without performing
EAT. Thus, future prospective studies including a control groupand collaborating with otolaryngologists and nephrologists mustbe performed. In this study, not all patients showed a reductionin the urinary occult blood level with the addition of EAT. The
reason for no improvement in the urinary occult blood level inpatients after tonsillectomy, steroid pulse therapy, and EAT is still
not known. Lastly, it is yet to be confirmed if additional steroid
pulses are the only option for treatment. After tonsillectomy and/or intravenous steroid pulse therapy, the epipharyngeal findings ofpatients temporarily improved. Sakamoto et al. reported the local
epipharyngeal findings in seven patients before and after pulse
therapy [27]. Nevertheless, future studies should be conducted tovalidate how epipharyngeal findings change over the course of IgAN
treatment. In conclusion, the urinary findings of 19 patients treateduntil the end of the study improved with tonsillectomy + pulse
therapy with EAT. Group B had a significantly faster improvement
in urine freshness than group A. This result might be attributed to
the fact that the site of glomerulo vasculitis focal inflammation ingroup B was only the nasopharynx. Therefore, I believe that thechronic epipharyngitis, which is thought to be the cause of the
focal inflammation, was treated with a therapeutic approach andthat the chronic epipharyngitis was considerably alleviated by
EAT, consequently relieving urine occult blood in patients withIgA nephropathy. Hence, EAT can be an additional treatment forpatients with IgAN. If there is a need to limit patients, EAT is better
indicated for group B.

Citation: Manabu Mogitate*. Epipharyngeal Abrasive Therapy for Patients with Immunoglobulin A Nephropathy: A Retrospective Study.
Sch J Oto 8(3)-2022. SJO. MS.ID.000286. DOI: 10.32474/SJO.2022.08.000286.

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Acknowledgment and Funding Source
I express my sincere gratitude to Dr. Hirobumi Ito for his
suggestions on the clinical practice of chronic epipharyngitis. I wish
to thank Yosuke Sasaki of the SATISTA Corporation for his statisticalanalysis. I would like to thank Editage (www.editage.com) for
English language editing. No funding was received for this study.

Meeting Information

This study was presented at the 120th Annual Meeting of the
Oto-Rhino-Laryngological Society of Japan, Osaka City, Japan, May
9th, 2019.

Conflicts of Interest

No conflicts of interest are declared by the authors.

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Citation: Manabu Mogitate*. Epipharyngeal Abrasive Therapy for Patients with Immunoglobulin A Nephropathy: A Retrospective Study.
Sch J Oto 8(3)-2022. SJO. MS.ID.000286. DOI: 10.32474/SJO.2022.08.000286.

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