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 Table of Contents  
ORIGINAL ARTICLE
Year : 2020  |  Volume : 9  |  Issue : 2  |  Page : 153-158

Primary fungal laryngitis: Our experiences at a tertiary care teaching hospital of Eastern India


1 Department of Otorhinolaryngology, IMS and SUM Hospital, Siksha “O” Anusandhan University (Deemed to be), Bhubaneswar, Odisha, India
2 Department of Oral Pathology and Microbiology, IDS, Siksha “O” Anusandhan University (Deemed to be), Bhubaneswar, Odisha, India

Date of Submission21-Feb-2020
Date of Decision04-Mar-2020
Date of Acceptance05-Mar-2020
Date of Web Publication9-Apr-2020

Correspondence Address:
Santosh Kumar Swain
Otorhinolaryngology, IMS and SUM Hospital, Siksha “O” Anusandhan University (Deemed to be) Bhubaneswar, Odisha
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/ijhas.IJHAS_16_20

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  Abstract 


INTRODUCTION: Primary fungal laryngitis is a fungal infection of the larynx without affecting the other body parts such as the lungs, pharynx, and oral cavity. It is an extremely rare clinical entity. Hoarseness of the voice is common clinical presentations.
OBJECTIVE: This study aimed to evaluate the etiology, clinical presentations, diagnosis, and treatment of primary fungal laryngitis at a tertiary care teaching hospital in Eastern India.
MATERIALS AND METHODS: This is a retrospective study of seven cases of primary fungal laryngitis managed between 2014 and 2019. The detailed etiology, clinical presentations, investigations, and treatment of primary fungal laryngitis patients were studied.
RESULTS: Primary fungal laryngitis is common among males with a mean age ranging from 15 to 63 years. There were five male and two female patients. The most common clinical symptom was hoarseness of voice (n = 7), dry irritating cough (n = 2), odynophagia (n = 1), discomfort in throat (n = 1), and dyspnea (n = 1). Laryngoscopic pictures of primary fungal laryngitis included leukoplakic lesions (n = 3), ulcerative lesions (n = 1), polypoidal lesions (n = 1), and nonspecific lesions (n = 2). Histopathological examination is confirmatory for the diagnosis. All the patients had taken antifungal treatment for 3–4 weeks after confirmation of the diagnosis.
CONCLUSION: The diagnosis of the primary fungal laryngitis is often overlooked and delayed among patients, as it is usually evident among immunocompromised patients. It often confuses with certain laryngeal diseases such as granulomatous diseases, leukoplakia, and malignancy. Delayed diagnosis and treatment will lead to high morbidity and mortality of the patients.

Keywords: Antifungal treatment, Aspergillus, hoarseness of voice, larynx, primary fungal laryngitis


How to cite this article:
Swain SK, Debta P, Shajahan N. Primary fungal laryngitis: Our experiences at a tertiary care teaching hospital of Eastern India. Int J Health Allied Sci 2020;9:153-8

How to cite this URL:
Swain SK, Debta P, Shajahan N. Primary fungal laryngitis: Our experiences at a tertiary care teaching hospital of Eastern India. Int J Health Allied Sci [serial online] 2020 [cited 2020 May 30];9:153-8. Available from: http://www.ijhas.in/text.asp?2020/9/2/153/282133




  Introduction Top


Fungal infections of the respiratory tract are a common incidence, whereas an isolated fungal infection of the larynx is a rare clinical incidence. Primary fungal laryngitis among immunocompetent patients is an extremely rare clinical entity. The larynx is an uncommon site for fungal infections of the body, and fungal laryngitis often presents with nonspecific clinical symptoms and misdiagnosed with certain laryngeal diseases such as leukoplakia and other granulomatous lesions of the larynx.[1] Clinical conditions such as prolonged use of antibiotics, inhaled steroids, and laryngopharyngeal reflux (LPR) can predispose to fungal infections of the larynx. Patients usually present with hoarseness of voice, odynophagia, and dyspnea due to laryngeal edema and granulations. The fungal laryngitis often mimics with granulomatous disease, gastroesophageal reflux disease, and malignant lesions.[2] Common fungi causing laryngitis are Candida, aspergillosis, cryptococcal, histoplasmosis, and blastomycosis.[3] The clinical presentations of primary fungal laryngitis are non-specific and also mimics to other laryngeal lesions, so it may be misdiagnosed and leading to the inappropriate treatment. Clinician and otorhinolaryngologist should be familiar with clinical presentations, diagnosis, and treatment of fungal infections at the uncommon site such as the larynx. To minimize the misdiagnosis and late treatment of primary fungal laryngitis, we had performed this study by retrospective analysis of the etiology, clinical presentations, investigations, and treatment.


  Materials and Methods Top


A total of 7 patients of primary fungal laryngitis with age range from 15 to 63 years were examined at the outpatient department of otorhinolaryngology between January 2014 and December 2019. Of the seven patients, five were male and two were female. This study was approved by the Institutional Ethical committee and consent of all participant patients was obtained for this study. A detail clinical examination, investigations, and treatment were documented in each case. The patient details such as age, sex, addiction, and risk factors for facilitating primary fungal laryngitis were recorded. The investigations such as fiberoptic nasopharyngolaryngoscopy, histopathological examination, and fungal examinations were done in all cases. Different lesions of the larynx such as ulcerations, granulations, leukoplakia, and nonspecific type lesions were documented. Chest X-ray was done in all cases. Samples from the oral cavity and oropharynx were sent for fungal staining. Computed tomography (CT) of the neck was done in one case for assessment of laryngeal lesions and airway. After confirmation of the diagnosis, patients were immediately started with antifungal medication such as itraconazole for 3–4 weeks. Detail clinical presentations of each patient are described below.

Case-1

A 43-year-old lady attended the outpatient department of otolaryngology with complaints of hoarseness of voice and cough for 3 months. Fiberoptic nasopharyngolaryngoscopy showed whitish patches on bilateral vocal folds [Figure 1]. Both vocal cords were mobile. She was checked to rule out for any immunocompromised conditions and tuberculosis which were negative. She was a known case of diabetes mellitus under treatment. This patient was planned for microlaryngoscopy and biopsy, and intraoperative findings revealed whitish patches at the anterior part of the vocal cords extending into the ventricular area which bleeds on touch. The whitish patches were stripped and sent for histopathological examination. Histopathological examination showed nonspecific keratosis with fungal hyphae of Aspergillus fumigatus. The patient was administered oral itraconazole 100 mg twice daily for 3 weeks postoperatively. The patient showed symptomatic improvement after antifungal treatment. In follow-up checkup after 3 months, laryngoscopy examination showed complete resolution of symptoms and signs with normal findings of both the vocal folds.
Figure 1: Fiberoptic nasopharyngolaryngoscopy showing whitish patches on bilateral vocal cords

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Case-2

A 63-year-old female attended the outpatient department of otolaryngology for complaints of change in voice and burning sensation in the throat with painful swallowing for 1 month. She was a HIV-positive patient. On indirect laryngoscopy (IDL) examination, it revealed congested vocal folds, epiglottis, and arytenoids. There were ulcerative lesions with whitish patch at the anterior part of both the vocal folds. The patient was not responded to antibiotics and other conservative treatment. She was planned for biopsy where the histopathological report revealed fungal hyphae. The diagnosis of fungal infection was done with KOH staining (Septate fungus). She was started with oral itraconazole 100 mg twice daily for 3 weeks. After the treatment, it revealed complete resolution of signs and symptoms at 1 month. During follow-up visit after 3 months of treatment, laryngeal examination revealed normal larynx.

Case-3

A 15-year-old boy attended the outpatient department of otorhinolaryngology with complaints of hoarseness of voice for 3 months. His otorhinolaryngology examination was unremarkable, except videolaryngoscopy revealed keratotic whitish patches over the anterior part of both the vocal folds. Bilateral vocal folds were mobile. The patient had no history of immunosuppression but a known case of bronchial asthma under treatment with inhaled corticosteroids for 2 years. The patient was investigated to check for tuberculosis, immunodeficiency, and diabetes which were negative. Microlaryngeal surgery and biopsy was done under general anesthesia. Intraoperative findings showed that both the vocal cords were edematous and irregular with whitish patch over it. The whitish patch was stripped and sent for histopathological examination which revealed keratosis with inflammatory changes and Aspergillus ball [Figure 2]. The culture in Sabouraud Dextrose Agar (SDA) for 4 days showed bluish-green velvety growth and powdery surface which confirmed A. fumigatus [Figure 3]a. The patient was administered antifungal drugs such as itraconazole 100 mg twice daily for 3 weeks. The patient improved symptomatically after completion of full course of itraconazole.
Figure 2: Histopathological examination (HPE) showing chronic inflammation in the subepithelial region of the vocal cords along with fungal balls consisting of thin septate hyphae with acute angle confirming aspergillosis (H and E; ×400)

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Figure 3: (a) Microscopic view of 48-h culture of Aspergillus (lactophenol cotton blue staining, ×400); (b) Candida albicans in Gram staining

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Case-4

A 31-year-old man attended the outpatient department of otorhinolaryngology with complaints of hoarseness of voice for 2 months. IDL examination showed bilateral thickened vocal folds. He had no history of immunosuppression. He was examined to rule out immunodeficiency, diabetes, and tuberculosis. He was a known alcoholic for 3 years. He was planned for microlaryngeal surgery and biopsy under general anesthesia. The thickened and irregular tissues from bilateral vocal folds were stripped and sent for histopathological examination. The histopathological examinations revealed inflammatory cells and Aspergillus ball. The sample was also sent for culture in SDA for 4 days which showed bluish green and velvety growth which confirmed A. fumigatus. The patient was treated with itraconazole 100 mg twice daily for 3 weeks. The patient improved symptomatically after completion of itraconazole course.

Case-5

A 45-year-old man presented with change in voice and foreign-body sensation in the throat for 4 months and had treated from local physicians for reflux laryngitis with no relief of the symptoms. He had habit of drinking alcohols for 5 years. Fiberoptic nasopharyngolaryngoscopy showed a raised irregular white patch with erythematous surrounding in anterior two-third of the vocal cord. The conservative treatments for laryngitis including antibiotics often fail to relieve the symptoms. Swab was taken from larynx in awake after spraying with 4% xylocaine. Candida albicans were identified in Gram staining [Figure 3]b. We started antifungal itraconazole 100 mg twice daily for 3 weeks after confirmation from Gram staining. He showed symptomatically improvement within 1 week. Posttreatment laryngoscopy examination showed complete resolution with normal voice quality.

Case-6

A 52-year-old male with no history of immunodeficiency presented with hoarseness of voice and dyspnea for 3 months which progressively worsening. He was a teacher by profession and had history of voice abuse. He had also history of prolonged use of broad-spectrum antibiotics from local physicians. He was a known case of diabetes mellitus under treatment. Fiberoptic nasopharyngolaryngoscopy revealed raised whitish-to-gray mass on the right vocal folds. Detail examinations of the head and neck were within the normal limit. He had undergone direct laryngoscopy under general anesthesia for biopsy. The histopathological examination showed numerous septate fungal hyphae with branching at an angle of 45°, i.e., Aspergillus. The polymerase chain reaction identified that agent was A. fumigatus. The patient was treated with oral itraconazole 100 mg twice daily for 3 weeks along with instructions for good vocal hygiene. The voice quality becomes normal after 3-week treatment. There was no evidence of recurrence after 3 months and laryngeal examination was within the normal limit.

Case-7

A 55-year-old male presented with complaints of progressive hoarseness of voice for 4 months. He had no history of tuberculosis, voice abuse, alcoholics, or laryngeal trauma. There was no history of prolonged steroid use or immunosuppressant use. He had habit of smoking for 15 years. There was no history of recurrent bacterial, viral, or fungal infections. General examinations and systemic examinations were within the normal limit. IDL showed whitish plaque-like lesion on the vocal folds with some irregularities on the interarytenoids area and vocal process. Both the vocal cords were mobile with adequate airway. Chest X-ray showed no abnormality. Microlaryngoscopy and biopsy were done under general anesthesia. Microscopic examination with hematoxylin and eosin stain showed septate fungal hyphae with dichotomous branching pattern at acute angle. Fungal culture with SDA revealed growth of velvety, green, and powdery colonies highly suggestive of A. fumigatus. He was treated with oral itraconazole 100 mg twice daily for 1 month. There was a dramatic improvement after this antifungal treatment. Further, 1-year follow-up did not show any recurrence.


  Results Top


There are seven patients diagnosed with primary fungal laryngitis during January 2013–August 2018. The age of all patients in this study ranged from 15 to 63 years. There were five males and two females in this study [Table 1]. Of seven patients, one had habit of chronic inhaling steroids, one had habit of smoking, and two had habit of drinking alcohol. There was no history of fungal infections among any family members. One patient had bronchial asthma, two had diabetes mellitus, and one had HIV. The most common clinical symptom was hoarseness of voice (n = 7), dry irritating cough (n = 2), odynophagia (n = 1), discomfort in the throat (n = 1), and dyspnea (n = 1) [Table 1]. Dyspnea was seen in patients showing thickened and advanced stage of primary fungal laryngitis. The sites for the lesions were true vocal cords/vocal folds (n = 6), arytenoids (n = 2), epiglottis (n = 1), and false cords (n = 1) [Table 1]. The different laryngoscopy pictures for primary fungal laryngitis in this study included leukoplakic lesions (n = 3), ulcerative lesions (n = 1), polypoidal lesions (n = 1) and nonspecific lesions (n = 2) [Table 2]. All patients showed normal chest X-ray. One patient had undergone CT scan of the neck showing thickening of the vocal cord and narrowing of the glottic airway. All patients had undergone biopsy and histopathological examinations except case 5 where swab was taken from the larynx after spraying 4% xylocaine. The histopathological examinations confirmed the diagnosis of fungal laryngitis. Of seven cases, Aspergillus was identified in five cases and Candida in two cases. All the seven patients were treated with antifungal treatment with itraconazole for 3 weeks. No serious side effects were observed during the treatment. All the patients were completely cured after course of antifungal treatment.
Table 1: Clinical profile of the patients of primary fungal laryngitis

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Table 2: Types of lesions in the larynx

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  Discussion Top


Fungal laryngitis often occurs in association with bronchopulmonary fungal infections. It is a common clinical entity among immunocompromised patients; however, the primary fungal infections of the larynx are extremely rare one.[4] Almost all fungal infections of the larynx are secondary to pulmonary or oropharyngeal infections.[5] In this study, no pulmonary or oropharyngeal fungal infections evidenced. Aspergillus and Candida are often associated with fungal laryngitis.[6] One study suggests that Candida is the most common agent causing fungal laryngitis.[7] In this study, Aspergillus is the most common agent associated with primary fungal laryngitis. Fungal laryngitis often mimics to granulomatous diseases, LPR disease, leukoplakia, and malignancy.[8] Low host immunity and impaired protective mucosal barrier of the larynx may lead to infections of the larynx.[9] Prolonged use of inhaled steroids is an important predisposing factor for primary fungal laryngitis. LPR may cause laryngeal mucosal injury through retrograde acid transit via the esophagus, and prolonged use of antibiotic may lower the bacterial burden of the larynx, so predisposing for fungal laryngitis.[10] There are different predisposing factors responsible for developing fungal laryngitis, for example, diabetes mellitus, immunosuppressive medications, immunodeficiency, and nutritional deficiency. In this study, one patient had bronchial asthma, two had diabetes mellitus, and one had HIV of seven cases. Certain conditions affect the mucosal barriers such as prior radiotherapy, gastroesophageal reflux disorders, inhaled corticosteroids, smoking, and trauma.[11] In case of inhaled corticosteroid therapy, the substantial proportion of molecules deposited in the airway when inhaled via dry-powered forms. Inhaled corticosteroids are often augmenting colonization of the epithelial surfaces and commonly cause fungal laryngitis and oropharyngeal candidiasis.[12] In our study, of seven cases, one had habit of chronic inhaling steroids, one had habit of smoking, and two had habit of drinking alcohol. Common clinical presentations of fungal laryngitis are variable and are hoarseness, dysphagia, dysphonia, stridor, odynophagia, and respiratory distress. The clinical spectrum ranges from localized allergic response to invasive infection. The most common symptom in fungal laryngitis is hoarseness of voice for several months as in this study. The endoscopic picture of the laryngeal lesions appear as different types of pathology such as erythematous lesion, edematous lesion and leukoplakia. In fungal laryngitis, videolaryngoscopy reveals erythema, edema, hyperkeratosis, adherent white plaques, shallow ulcerations, and gray or white pseudomembranes formation over the vocal cords.[7] Although strobovideolaryngoscopy is nonspecific, it gives important data on the integration of mucosal waves of the vocal folds. In the larynx, mucosal edema and erythema even after sufficient therapy for laryngopharyngeal diseases need prompt consideration for fungal laryngitis.[7] The fungal laryngitis often mimics to leukoplakia, carcinoma, LPR disease, and granulomatous disease.[13] Definitive diagnosis of fungal laryngitis is done by the demonstration of fungal spores, hyphae, or pseudohyphae either by KOH staining, culture, or tissue biopsy. At early stage of the disease, biopsy helps to exclude the malignancy and its progression. The characteristic features of histopathological examination are termed as pseudoepitheliomatous hyperplasia.[3] Direct microlaryngoscopy with KOH preparation of the tissue shows 45° Y-shaped dichotomous branching, septate hyphae. Some portion of the tissue can be cultures on SDA. The suspicion of fungal lesion should be informed to the pathologist for appropriate staining as diagnosis could be missed. Histopathological examination of the tissue is easy and quick way to identify the fungal laryngitis. Gomori Methenamine Silver and periodic acid–Schiff are commonly used stains to find fungi in the cytological specimen. Fungi inside the tissue may appear as hyphae, budding yeast, endosporulating spherules, or mixture of these forms.[14] The diagnosis of fungus is confirmed by seeing fungal spores, hyphae, or pseudohyphae either by culture or tissue biopsy or KOH stain. The Aspergillus hyphae appear as basophilic with hematoxylin and eosin stain. Prompt treatment and appropriate measures will prevent the morbidity of fungal laryngitis. It is usually treated by antifungal drugs and eliminations of risk factors.[15] The first-line antifungal agents differ from local to systemic. Systemic oral antifungal agents such as itraconazole or fluconazole are given daily for 3 or 4 weeks. In immunocompromised patients with noninvasive lesions, first-line treatment is the oral antifungal agent, whereas intravenous amphotericin B is useful in patients with significant tissue invasion. In our case, tablet itraconazole 100 mg given twice a day for 3 to 4 weeks showed symptomatic improvement with resolution of the lesions over the vocal cords. The treatment duration ranges from 1 week to 1 month depending on the extent of the clinical improvement. Regular videolaryngoscopy is advised for seeing any recurrence which is not an uncommon incidence.[16] Early diagnosis and treatment of fungal laryngitis is important for preventing the spread of infection and systemic involvement. Inadequate treatment or misdiagnosis of this lesion can lead to impaired functioning of the vocal cords and leads to disability. Sometimes, a patient of bronchial asthma is used to inhale corticosteroids for prolonged period. Inhalational corticosteroids are easily available as over-the-counter drugs and patients are using even without prescribed by pulmonologists. Inhalation corticosteroids should be stopped or avoided in case of fungal laryngitis for preventing further spread of the lesions.[17] Although primary fungal laryngitis has nonspecific clinical presentations, it is very important to have a high index of suspiciousness to rule out fungal lesion in the larynx as this is a curable disease.


  Conclusion Top


Diagnosis of primary fungal laryngitis among immunocompetent patients is usually overlooked as it often mimics to leukoplakia and other granulomatous diseases of the larynx. A high index of suspicion is needed for diagnosis in case of persistent laryngitis failed with conservative treatment. Biopsy from the laryngeal lesion is the confirmatory for diagnosis. Prolonged treatment with antifungal and avoidance of predisposing factors are helpful for the treatment of primary fungal laryngitis.

Study limitation

This study has a relatively small sample size (due to rarity of this clinical entity) and may limit the outcome of the above interpretation. However, the outcome of this study will give encouragement to further research.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

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Chandran SK, Lyons KM, Venu DM, Sataloff RT. Fungal laryngitis. Laryngoscopic clinic. Ear Nose Throat J 2009;88:1026-37.  Back to cited text no. 13
    
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Haque AK, McGinnis MR. Fungal infections. In: Dail and Hammar's Pulmonary Pathology. Ch. 10. New York: Springer; 2008. p. 349-408.  Back to cited text no. 14
    
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Swain SK, Sahu MC. Isolated vocal cord aspergillosis in a professional flute player – A case report. Pol Ann Med 2016;23:161-4.  Back to cited text no. 15
    
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Nunes FP, Bishop T, Prasad ML, Madison JM, Kim DY. Laryngeal candidiasisg malignancy. Laryngoscope 2008;118:1957-9.  Back to cited text no. 16
    
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Swain SK, Nahak B, Sahu MC. Fungal laryngitis in asthmatic boy treated with inhaltory corticosteroids: A case report. Pediatr Pol 2017;92:453-6.  Back to cited text no. 17
    


    Figures

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    Tables

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