Schizophyllum radiatum: An uncommon culprit of invasive fungal rhinosinusitis in an immunocompetent patient – A case report from India

Abstract

Schizophyllum species are emerging human respiratory pathogens. We report India's likely first case of invasive fungal rhinosinusitis by Schizophyllum radiatum. A 32-year-old healthy woman presented with bilateral nasal discharge. Microscopic examination of the sinus aspirate showed septate hyaline hyphae and culture yielded fungal growth with sterile hyphae. The isolate was identified as S. radiatum by sequencing of the ITS region. This highlights the importance of genomic sequencing for the identification of non-sporulating molds.

1. Introduction

Fungal rhinosinusitis (FRS), a subtype of chronic rhinosinusitis (CRS) lasting for at least 12 weeks, is primarily driven by the ubiquitous presence of fungal spores in the environment [1]. It can be classified into non-invasive (NFRS) and invasive forms. NFRS, which generally affects immunocompetent individuals, presents in a more chronic manner, whereas invasive fungal rhinosinusitis, a more aggressive and often fatal condition, is seen predominantly in immunocompromised patients and results in significant morbidity and mortality [2].

While FRS is most commonly associated with species of Aspergillus and Mucorales, and other fungi such as Fusarium, Schizophyllum, Alternaria, Ulocladium, Curvularia, and Bipolaris are also known to cause infections [2,3].

Basidiomycetous molds are rarely identified as human pathogens due to challenges in identification and in distinguishing true infection from colonization. Schizophyllum, a member of sterile and/or arthroconidium-forming basidiomycetes, is one such rare mold. They are widely distributed in nature, with Schizophyllum commune being the most common species [4]. Infections have been reported in both immunocompromised and immunocompetent individuals [[5], [6], [7]].

Among the various clinical presentations, respiratory infections—including fungal rhinosinusitis—have been most commonly associated with this fungal species. The majority of documented cases from various parts of the world primarily involve Schizophyllum commune infections. [[5], [6], [7], [8], [9], [10]]. To date, only a few clinical isolates of S.radiatum have been identified [4,11], primarily through strain sequencing. The role of S. radiatum in fungal rhinosinusitis is now being increasingly recognized and here, we report what is likely the first documented case of invasive fungal rhinosinusitis caused by S. radiatum in India.

2. Case

2.1. Clinical history

A 32-year-old non diabetic healthy woman without any known comorbidities presented to the Ear, Nose, and Throat (ENT) clinic with a six-month history of foul-smelling bilateral nasal discharge, accompanied by postnasal drip and episodes of persistent bilateral headache. She also reported bilateral frontal sinus tenderness. On ENT examination, findings were unremarkable except for a deviated nasal septum towards the right.

2.2. Investigations

Contrast enhanced magnetic resonance imaging of brain (CE-MRI brain) (Fig. 1) was performed and findings were suggestive of invasive fungal sphenoid sinusitis. Based on the clinical history and radiological findings, the patient was diagnosed with allergic fungal rhinosinusitis affecting the right sphenoid sinus. For definitive management, she underwent a right-sided functional endoscopic sinus surgery (FESS) under general anesthesia. Intraoperatively, the right sinus was found to be filled with thick, cheesy material, which was cleared and sent for mycological studies.

Fig. 1.

Contrast enhanced MRI Brain: Mass like thickening of the mucosa involving the right posterior ethmoid sinuses, extending to the sphenoid sinus; No intracranial extension; No extension to pharynx and to orbit (marked with arrow).

2.3. Mycological analysis

Direct microscopy of the sinus aspirate revealed thin, septate hyphae on a KOH mount (Fig. 2). Fungal culture on Sabouraud Dextrose Agar containing chloramphenicol (M1067, Himedia, India), incubated at 25 °C and 37 °C, showed confluent white, cottony, flat mold growth on day 3 (Fig. 3). Further microscopic examination, performed after slide culture using potato dextrose agar (PDA), showed thin septate hyphae without sporulation (Fig. 4).

Fig. 2.

KOH mount of sinus aspirate showing thin septate hyphae under 40× magnification (marked with arrow).

Fig. 3.

SDA growth of isolate on Day 3.

Fig. 4.

LPCB mount from slide culture showing clamp connection under 40× magnification. (marked with arrow).

Due to the absence of characteristic morphological features, the isolate was sent to the Advanced Mycology Diagnostic and Research Centre (ICMR – South Zone) at St. John's Medical College, Bangalore, Karnataka, India for further identification. Matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF-MS, Biomerieux) failed to provide conclusive identification. Hence, the isolate was subjected to sanger sequencing targeting the Internal Transcribed Spacer (ITS) 1 and 4 regions of ribosomal DNA. Sequence data was analyzed using pairwise comparison in the ISHAM database, revealing an 99.48 % identity with S. radiatum thereby confirming its identification as S. radiatum. Detailed sequence information is available in Supplemental Material S1.

2.4. Follow up

Postoperatively, based on KOH findings, the patient was started on oral Itraconazole (100 mg twice daily) for a total duration of four weeks. Diagnostic nasal endoscopy (DNE) on post operative day 14 & at six month follow up showed normal sinonasal mucosa without evidence of residual disease.

3. Discussion

We present a rare case of invasive fungal rhinosinusitis in a young immunocompetent female patient, caused by S.radiatum. Due to its unusual morphological characteristics, identification was confirmed through sequence analysis.

Schizophyllum species are environmental basidiomycetous fungi found widely in nature, with S. commune being the most common [4,5]. In recent years, S. commune has been recognized as a rare cause of fungal infections in humans [4,10]. In contrast, infections caused by S. radiatum are extremely uncommon. One of the few reports, by Siqueira et al. (2016), highlighted the emergence of S. radiatum as a respiratory pathogen, particularly affecting the sinuses [4]. Here this case report also presents the isolation of S. radiatum, likely marking the first documented instance of this infection in India.

Schizophyllum primarily causes respiratory tract infections, more commonly bronchopulmonary infections and fungal sinusitis, accounting for approximately 90 % of reported cases [10].The predilection for the respiratory tract aligns with the airborne transmission of basidiospores, which are easily inhaled. Several factors influence disease progression, including the host's immune status, anatomical abnormalities such as a deviated nasal septum, corticosteroid use, and prolonged exposure to fungal spores [4]. In our case, the presence of a right-sided deviated nasal septum may have contributed to the development of the infection.

According to the study by Taghian E et al., non-invasive FRS is typically observed in immunocompetent individuals, whereas invasive FRS with a chronic course—associated with higher morbidity and mortality—is more common in immunocompromised patients [3]. Contrary to these findings, our study documents a case of invasive fungal rhinosinusitis in a young immunocompetent female patient with no known comorbidities.

Currently, only a few Schizophyllum species (S. commune, S. fasciatum, S. radiatum, and S. umbrinum) have been documented in public culture collections. Key diagnostic features, such as clamp connections on hyphae and the development of fruiting bodies, are challenging to observe in clinical settings. Many clinical isolates present only with white cottony colonies and droplets of exudate, which are not distinctive and therefore not useful for identifying the species or genus [4].

To address these diagnostic challenges, many molecular techniques have been developed for successful discrimination of these basidiomycetous molds. A study by Siqueria et al. (2016) examined genetic markers such as the Internal Transcribed Spacer (ITS) and D1/D2 regions of the LSU, as well as EF-1∂ and RPB2 regions, for Schizophyllum species identification. The study suggested that LSU, EF-1∂, and RPB2 markers are more effective in differentiating S. radiatum from S. commune than the ITS region [11].

Among S.commune isolates, studies by A Chowdhary et al. and Gonzalez et al. demonstrated low MIC ⁄ MEC's for amphotericin B, caspofungin, micafungin, anidulafungin and all of the azoles including the newer ones like isavuconazole [9,12]. Study by Siqueira et al. also noted better in vitro antifungal susceptibility for S. commune isolates whereas significant variability in antifungal susceptibility was noted among S. radiatum isolates, especially to azoles and terbinafine [4].

Our study highlights the critical need for greater awareness and precise molecular identification of rare yet clinically significant basidiomycetes in human infections, particularly in patients with chronic sinusitis resistant to standard treatment. Considering the potential for misidentification due to differences in genetic markers, further studies incorporating multiple gene targets and a larger number of specimens from diverse geographical regions are needed to enhance our understanding of this emerging fungal pathogen.

CRediT authorship contribution statement

Anuja George: Writing – original draft, Resources, Methodology, Formal analysis, Data curation. Rosmi Jose: Writing – review & editing, Supervision, Methodology, Formal analysis, Conceptualization. Chithra Valsan: Writing – review & editing, Visualization, Validation, Supervision, Conceptualization. Jayanthi Savio: Writing – review & editing, Validation, Software, Resources, Investigation. Priyadarshini A. Padaki: Validation, Software, Resources, Investigation. Ramesh Kumar: Writing – review & editing, Validation, Investigation.

Declaration of generative AI and AI-assisted technologies in the writing process

During the preparation of this work the author(s) used Chat GPT tool in order to modify the prepared content for a better language/grammar usage. After using this tool/service, the author(s) reviewed and edited the content as needed and take(s) full responsibility for the content of the publication.

Conflict of Interest

There are none.

Appendix A. Supplementary data

The following is the Supplementary data to this article.