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DOI: 10.2174/0250688202002022006, 2020, 1(2), 79-82

New Emirates Medical JournalContent list available at: https://newemiratesmedicaljournal.com

CASE REPORT

Recovery of Sense of Smell by Mepolizumab in a Patient with ChronicRhinosinusitis and Nasal Polyposis

Mohamed Abuzakouk1,*, Omar Ghorab1, Safieeldin Ghazala2 and Anastasios Hantzakos3

1Department of Allergy and Immunology, Cleveland Clinic Abu Dhabi, Abu Dhabi, UAE2Department of Imaging, Cleveland Clinic Abu Dhabi, Abu Dhabi, UAE3Department of Surgical Subspecialties, Cleveland Clinic Abu Dhabi, Abu Dhabi, UAE

Abstract:

Introduction:

To date, there is no permanent medical treatment for nasal polyposis and loss of sense of smell. Mepolizumab is an anti-IL-5 monoclonal antibodyapproved for the treatment of patients with eosinophilic asthma. It has been suggested that it is capable of improving olfactory dysfunction inpatients with chronic rhinosinusitis and nasal polyposis.

Case:

We present a 35-year-old Emirati male with progressively worsening rhinosinusitis, recurring nasal polyps and total loss of sense of smell. He wastreated with oral steroids, normal saline nasal sprays and all available topical steroids without significant or permanent symptom relief. He wascommenced on Mepolizumab, and upon receiving the 4th dose, he reported full recovery of his sense of smell.

Conclusion:

Mepolizumab appears to be very effective in treating loss of sense of smell. Further studies should be conducted to assess the efficacy andeffectiveness of Mepolizumab in patients with chronic rhinosinusitis, nasal polyposis and anosmia.

Keywords: Mepolizumab, Nasal polyps, Olfaction disorders, Sinusitis, Paranasal sinus diseases, Rhinosinusitis.

Article History Received: December 25, 2019 Revised: January 30, 2020 Accepted: February 03, 2020

1. INTRODUCTION

Chronic rhinitis with nasal polyposis is characterised bysymptoms such as nasal discharge, stuffiness, facial pressure orpain, cough from post-nasal drip, and olfactory dysfunction ortotal loss of sense of smell (anosmia) [1]. In inflammatoryconditions such as rhinitis, there are two components: aninflammatory component, and a conductive component, whichis the one in direct association with the olfactory neuro-epithelium [2]. Olfactory dysfunction in inflammatoryconditions can occur as a result of damage to the neuro-epithelium, due to local inflammation, that prevents odoursfrom reaching the cilia receptors found in the epithelium. Morespecifically, the neuro-epithelium is damaged as it becomesoedematous from the inflammatory process occurring, and theproducts of the inflammatory process cause damage to the

* Address correspondence to this author at the Department of Allergy andImmunology, Cleveland Clinic Abu Dhabi, Al Falah Street, Abu Dhabi, UAE;Tel: +971 529050223; E-mail: AbuzakM@clevelandclinicabudhabi.ae

olfactory neurons, thus preventing any transmission of synapticimpulses [2]. In addition to chronic rhinitis, there are otherconditions that have been proven to be associated witholfactory dysfunction, such as nasal polyposis, asthma, septaldeviation, turbinate hypertrophy, tobacco and allergic rhinitis[3]. Clinical treatment of olfactory dysfunction remains limitedand of temporary effect [3, 4]. One study has shown that anti-IL5 therapy (mepolizumab) is effective in patients with chronicrhinitis with nasal polyposis, and it has also resulted in asignificant improvement in olfactory function [5].

Recently, a case report was published, describing a patientsuffering from chronic rhinitis, nasal polyposis, asthma, andeosinophilia with olfactory dysfunction [6]. The patient wascommenced on nasal and injective corticosteroids, which wereunsuccessful in treating the loss in the sense of smell. As thepatient was a severe asthmatic, they fulfilled eligibility criteriafor Mepolizumab treatment, and after 4 months of treatment,the patient experienced full recovery of their sense of smell,with good control of their severe asthma.

80 Abuzakouk et al.

2. CASE NARRATIVE

The patient is a 35-year-old Emirati male attendingCleveland Clinic Abu Dhabi with longstanding and recurrentnasal polyps, hyposmia and nasal congestion. He has mildintermittent asthma and adverse reaction to oral Voltaren(Diclofenac Sodium), otherwise he has no personal or familyhistory of note. He has a history of Functional EndoscopicSinus Surgery (FESS), carried out in 2008 (Fig. 1), with partialimprovement. His symptoms have become progressively worseand he underwent further FESS in 2017 for nasal polypremoval. A year later, he suffered from significant nasalmucosal swelling with polypoid inflammation, mostly on theleft side with the almost total loss of sense of smell. He wastreated over the course of his disease with severalantihistamines, montelukast, short courses of oral steroids,normal saline nasal sprays and almost all available topicalsteroids without any significant or permanent symptomaticrelief. Furthermore, he was commenced on subcutaneousimmunotherapy with environmental allergen vaccines withoutany improvement. His nasal symptoms, mainly anosmia,caused significant emotional stress and impressment andaffected his daily activity and social life. He was looking for apermanent cure to resolve his nasal symptoms and recover hissense of smell.

The patient underwent extensive allergy assessment,including blood tests and skin prick tests that showed positivityfor tree, grass, and weed pollen. The nasal polyp score of thepatient was Grade 2, bilaterally, according to Hadley’s ClinicalScoring System of Nasal Polyposis. His full blood count

showed no eosinophilia. Olfactory dysfunction wasinvestigated via the Visual Analogue Scale (VAS).

He was offered a trial of mepolizumab as it was the onlybiologic available in our hospital back then. The patientconsented to receive the anti-IL5 biologic, fully aware that ithas not been approved for any nasal or sinus disorder. It wasagreed that he will receive 100mg of mepolizumabsubcutaneously every 4 weeks for a trial period of 4-6 months.

The patient’s sense of smell started to improve after the 1stdose and by the 4th dose, he reported full recovery of his senseof smell, with almost total relief of nasal symptoms, which alsoreflected on his VAS score (Fig. 2). He is currently doing verywell and almost asymptomatic. He stopped all his medications,including immunotherapy, as he felt very well after receivingmepolizumab. The disease state was clinically investigated viaComputer Tomography (CT) of the paranasal sinuses (Fig. 3).Before treatment, CT showed significant mucosal thickening ofthe bilateral of the maxillary sinuses in the axial plane, andsignificant mucosal thickening of the maxillary sinuses, nasalcavities, and ethmoids in the coronal plane. Three months aftertreatment, CT showed much improved mucosal thickening ofthe bilateral of the maxillary sinuses with patency of the leftantrostomy opening in the axial plane and much improvedmucosal thickening of both maxillary sinuses and ethmoidswith patency of the left antrostomy opening in the coronalplane. The drug was administered at our healthcare facility, andso adherence to the drug was monitored accordingly. Therewere no adverse or unanticipated events reported upon drugadministration.

Fig. (1). Timeline and associated treatment outcomes.

All failed to improve

hyposmia + nasal

symptoms

Temporary

improvement of

symptoms

Nasal congestion

Hyposmia

Possible nasal Functional Endoscopic

Sinus Surgery

Recurrence of nasal

symptoms + asthma

Functional Endoscopic

Sinus Surgery +

Fexofenadine, Montelukast,

Mometasone furoate nasal

spray

- Anti-histamines

- Short course of

oral

corticosteroids

- Subcutaneous

immunotherapy

Nasal congestion

Intermittent hyposmia

Sinus polypoid changes on

left side

First dose of Mepolizumab,

100mg SC

2008

2015

2017

2018

2019

Fourth dose of Mepolizumab

Full recovery of

hyposmia + no

nasal symptoms

+ good control of

asthma.

Patient

discontinued all

other therapies

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Recovery of Sense of Smell by Mepolizumab 81

Fig. (2). Improvement in smell after mepolizumab therapy.

Fig. (3). Computer tomography comparison before and after treatment in axial and coronal planes.

3. DISCUSSION

We report an Emirati patient with longstanding andrecurrent nasal polyps, anosmia and nasal congestion who fullyrecovered his sense of smell after treatment with mepolizumab.Mepolizumab and Omalizumab are thought to improve nasalpolyposis, as shown in a meta-analysis of five studiescomparing the treatment outcome of biological therapy withplacebo, quantified by the nasal polyp score [5]. The anti-IL-5monoclonal antibody mepolizumab is indicated in the severeeosinophilic asthma phenotype [7] and has not been licensed to

treat other eosinophil driven diseases. However, there is noreason to believe that it will not be as effective in otherconditions, including chronic rhinosinusitis with nasalpolyposis. There is only one case report similar to ours of apatient suffering from chronic rhinitis, nasal polyposis, asthma,eosinophilia with olfactory dysfunction, that displayedimprovement in olfaction after treatment with mepolizumab[6]. Our patient showed no blood eosinophilia; however hisremarkable improvement on mepolizumab raises the possibilitythat his inflammatory process is eosinophil driven and suggeststhat local eosinophilia may have played a role in the disease

0

10

20

30

40

50

60

70

80

90

100

1 2 3 4

VA

S S

core

Number of Mepolizumab doses

New Emirates Medical Journal, 2020, Volume 1, Number 2

82 Abuzakouk et al.

process. Furthermore, the patient did not respond toimmunotherapy, suggesting that his symptoms are unlikely tobe driven by a Type 1 hypersensitivity reaction, furtherwarranting the use of Mepolizumab.

CONCLUSION

Dupilumab has only recently been approved by the FDA asbiologic therapy for the treatment of chronic rhinosinusitis withnasal polyposis [8]. Mepolizumab appears to be very effectivein treating loss of sense of smell. We recommend that studiesof patients with chronic rhinitis and nasal polyposis withanosmia/hyposmia should be conducted to assess the efficacyand effectiveness of mepolizumab in treating olfactorydysfunction in these patients.

PATIENT PERSPECTIVE

“I fully consented to receiving Mepolizumab to treat myanosmia, for a trial period of 4-6 months, with a dose of 100mgper injection, subcutaneously. I suffered no adverse eventsduring or after the injection procedure. The drug has fullytreated my anosmia, as well as my nasal symptoms, withcontrol of my asthma. I am willing to continue on the drug fora longer time period.”

ETHICS APPROVAL AND CONSENT TO PARTI-CIPATE

Not applicable.

HUMAN AND ANIMAL RIGHTS

Not applicable.

CONSENT FOR PUBLICATION

Consent to disclosure of clinical data and radiologicalimages was obtained from the patient.

STANDARD FOR REPORTING

The CARE guidelines were carefully followed for writing

this case report.

FUNDING

None.

CONFLICT OF INTEREST

The authors declare no conflict of interest, financial orotherwise.

ACKNOWLEDGEMENTS

None.

REFERENCES

Fokkens W, Lund V, Mullol J. European position paper on[1]rhinosinusitis and nasal polyps 2007. Rhinol Suppl 2007; 20: 1-136.[PMID: 17844873]Mott AE, Leopold DA. Disorders in taste and smell. Med Clin North[2]Am 1991; 75(6): 1321-53.[http://dx.doi.org/10.1016/S0025-7125(16)30391-1] [PMID: 1943323]Sánchez-Vallecillo MV, Fraire ME, Baena-Cagnani C, Zernotti ME.[3]Olfactory dysfunction in patients with chronic rhinosinusitis. Int JOtolaryngol 2012; 2012327206[http://dx.doi.org/10.1155/2012/327206] [PMID: 22685462]Doty RL, Mishra A. Olfaction and its alteration by nasal obstruction,[4]rhinitis, and rhinosinusitis. Laryngoscope 2001; 111(3): 409-23.[http://dx.doi.org/10.1097/00005537-200103000-00008] [PMID:11224769]Rivero A, Liang J. Anti-IgE and anti-IL5 biologic therapy in the[5]treatment of nasal polyposis: a systematic review and meta-analysis.Ann Otol Rhinol Laryngol 2017; 126(11): 739-47.[http://dx.doi.org/10.1177/0003489417731782] [PMID: 28918644]Cavaliere C, Incorvaia C, Frati F, et al. Recovery of smell sense loss[6]by mepolizumab in a patient allergic to Dermatophagoides andaffected by chronic rhinosinusitis with nasal polyps. Clin Mol Allergy2019; 17(1): 3.[http://dx.doi.org/10.1186/s12948-019-0106-2] [PMID: 30804712]Albers FC, Müllerová H, Gunsoy NB, et al. Biologic treatment[7]eligibility for real-world patients with severe asthma: The IDEALstudy. J Asthma 2018; 55(2): 152-60.[http://dx.doi.org/10.1080/02770903.2017.1322611] [PMID:28622052]FDA approves dupixent (dupilumab) for chronic rhinosinusitis with[8]nasal polyposis regeneron 2019. [accessed: 26 Jun, 2019]. Availablefrom:https://investor.regeneron.com/news-releases/news-release-details/fda-approves-dupixentr-dupilumab-chronic-rhinosinusitis-nasal

© 2020 Abuzakouket al.

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New Emirates Medical Journal, 2020, Volume 1, Number 2