Sphenoid Sinusitis in an Immunocompetent Patient

Introduction

A. strictum, an environmental and saprophytic fungus, often leads to infections of plants and insects [1]. As a rare human opportunistic pathogen, A. strictum infection had been reported in several countries, including China [2]. Although A. strictum infection has been recognized and documented in the last 2 decades, the etiologic diagnosis is still challenging and there are no standard therapy guidelines for this disease. Moreover, this rare opportunistic infection can be life-threatening in some immunocompromised persons [3]. In recent years, several pathogens of fungal sinusitis have been reported [4–7]. Mohammadi et al [4] and Marglani et al [5] both mentioned that Aspergillus and Aspergillus fumigatus were the most common and causative agents of sinusitis. Various fungi, such as Aspergillus, Alternaria, Mucormycosis, Penicillium, and Bipolaris, can be isolated from the fungus ball [6]. Several reviews of fungal sinusitis in patients over the past 50 years show that Aspergillus flavus was one of the most frequently isolated pathogens [8,9] (Table 1). However, sphenoidal sinusitis caused by A. strictum is rarely reported. In this paper, we summarize the infection sites of A. strictum and the use of drugs for the treatment of the infections caused by this pathogen, which is important for the accurate diagnosis and treatment of fungal sphenoid sinusitis. We present such a case due to this fungus infection.

Case Report

REVIEW OF LITERATURE:

Case reports were searched in PubMed, Web of Science, Cochrane, and Embase up to December 2024. Search keywords and medical subject headings included ‘Acremonium strictum’, ‘A. strictum’ and ‘Acremonium strictum infection’. In recent years, a total of 9 cases [Turkey (n=3), India (n=2), Italy (n=1), UK (n=1), France (n=1), Spanish (n=1) and Toronto (n=1)] were reported, which are summarized in Table 2. The average age of patients was 56 years, and the male-to-female ratio was 1: 2. Reports of patients infected by A. strictum are mostly invasive [10–20], and mainly in those with poor immune function [11–13,16,18–20]. Among these cases, A. strictum infected the superficial parts, causing a variety of infections such as finger (toe) nail infection [10] and keratitis [11,12]. It also invaded the deep regions, leading to endocarditis [13], brain abscesses [14], and osteomyelitis [15], and sometimes it was found in peritoneal dialysis patients [16]. A. strictum can also induce osteomyelitis in people with normal immune systems [15].

Discussion

A. strictum is a Hyphomycetes fungus that often infect plants and insects. As an opportunistic pathogen, infection of humans by A. strictum is relatively rare. A. strictum can cause osteomyelitis in immunocompetent adults [15]. Some cases were diagnosed based on analysis of peritoneal dialysis fluid of patients [16,20]. A. strictum infective sphenoid sinusitis in an immunocompetent adult is also rare in clinical practice.

According to the results of the nasal endoscopy, the diagnosis of sphenoid sinusitis was confirmed, and the etiological examination revealed the presence of Aspergillus at the site of inflammation. Therefore, Aspergillus sphenoid sinusitis was considered. In most cases, endoscopic sinus surgery is effective for the removal of affected tissues, mucus, and polyps in fungal sphenoidal sinusitis; however, the infection relapses in some patients, especially in the elderly [4]. The European Position Paper on Rhinosinusitis and Nasal Polyps (EPOS) 2020 [21] emphasizes that endoscopic sinus surgery is only one part of the treatment strategy for chronic rhinosinusitis, and the main purpose of surgery is to create better conditions for local drug treatment, and continuous postoperative antimicrobial therapy is very important. According to the imaging data of the patient, the sphenoid sinus bone had uneven thickening and was accompanied by ethmoid sinus inflammation. Hence, this situation should be considered as a non-quiescent fungal infection, requiring antifungal therapy. If regular antifungal therapy is not carried out in time, the pathogen can spread to other organs and systems, with orbital and intracranial complications [22].

Timely diagnosis and corresponding treatment initiation determine disease progression and outcomes. CT and magnetic resonance image modalities can give the possible diagnosis of fungal sinusitis by characteristics of opacification, soft tissues, thickened mucosa, intralesional calcifications, and hyperdensity/T1 hyperintense in the affected sinus [23,24]. From our case, A. strictum infective rhinosinusitis was characterized by thickened mucosa, intralesional calcifications, and chronic osteomyelitis. The extensive sclerosis bone walls of the sinus without bone erosion on CT suggested a chronic and recurrent fungal sinusitis [25]. However, no definite imaging findings of A. strictum-related sinusitis have been reported until now, and radiological diagnosis of this patient could not provide further fungal species information. Frustratingly, the species cannot always be identified by microbial morphology. Reasons for identification failure include morphological similarity between Acremonium species and other molds such as Fusarium, and lack of experience. Therefore, it is difficult to make an appropriate diagnosis and relapses easily occur.

Fortunately, molecular biological identification, including molecular detection and mass spectrum identification, may be the best method for identifying filamentous fungus [3]. On the 10th day after admission for this case, the patient was diagnosed as A. strictum infection by 26S rRNA sequencing. Then, further cause-specific treatment could be provided.

Figure 5 illustrates a clinical path to diagnose rare fungal rhinosinusitis. This path may significantly enhance the diagnostic accuracy, reduce the detection time, and allow prompt intervention.

A. strictum infection is characterized by a long course of disease and is hard to completely cure. At present, there is no standard for A. strictum therapy. A. strictum may be poorly sensitive to conventional antifungal drugs, including amphotericin B and fluconazole, resulting in high morbidity and mortality [13]. Hence, researchers used multiple drug susceptibility studies on A. strictum and the results showed terbinafine, voriconazole, ciclopirox olamine, amorolfine, and posaconazole had good curative potential against A. strictum, amphotericin B and ketoconazole had limited effects, while itraconazole, sertaconazole, and fluconazole showed no antimicrobacterial activity against A. strictum [13,19]. Guarro et al [13] reported that Acremonium species were susceptible in vitro to amphotericin B (MIC=1.16 μg/ml), but resistant to 5-fluorocytosine (MIC >322.7 μg/ml), miconazole (MIC=20 μg/ml), ketoconazole (MIC >10 μg/ml), fluconazole (MIC >80 μg/ml), and itraconazole (MIC=6.4 μg/ml). Hitoto et al [19] found A. strictum isolated from the blood of the patient was sensitive to voriconazole (CMI50=2 μg/ml) and posaconazole (CMI50=1μg/ml), but was resistant to 5-flucytosine (CMI50 ≥64 μg/ml), amphotericin B (CMI50 ≥8 μg/ml), itraconazole (CMI50 ≥8 μg/ml), and caspofungin (CMI50 ≥8 μg/ml). Voriconazole, a triazole derivative with broad-spectrum antifungal activity, inhibits cytochrome P450-dependent enzyme 14-α-sterol demethylation, damages fungal membranes, and prevents fungal growth [26], and can be used for hosts with immunodeficiency or failure of immune response after therapy [27]. Our patient diagnosed with A. strictum-related rhinosinusitis was immediately treated with voriconazole. As expected, a good prognosis was obtained.

Conclusions

We report a rare case of A. strictum sphenoid sinusitis. This case highlights the necessity of developing effective and rapid detection methods for identifying fungal species in patients with chronic recurrent fungal rhinosinusitis. This would enable clinicians to implement timely and accurate treatments, minimize the misuse of antibiotics, and ultimately improve patient outcomes and prognoses.